Derivatives of p-substituted phenyl ester of pivalic acid

ABSTRACT

A derivative of general formula: ##STR1## wherein Y is --SO 2  -- or ##STR2## (i) R 1  and R 2 , which may the same or different, each represent, (1) --H, (2) C1-16 alkyl or (3) the formula: --X--A-- (R 4 )n wherein X is single-bond, --SO 2  --, C1-4 alkylene, C1-4 alkylene substituted by --COOH or ##STR3## --A-- is a pyridyl or pyrrolyl ring, n is 1˜5, R 4  is 1 --H or C1-8 alkyl, 2 C1-14 alkoxy, 3 C1-6 alkylthio, 4 --OH, halogen, --NO 2  or trihalomethyl, 5 the formula: --NR 41  R 42  wherein R 41  and R 42  each represents halogen or C1-4 alkyl, 6 tetrazole, 7 --SO 3  H or --CH 2  OH, 8 the formula: --SO 2  NR 41  R 42  9 the formula: --Z 41  --COOR 43  wherein Z 41  is single-bond, C1-4 alkylene or C2-4 alkenylene, R 43  is --H, C1-4 alkyl or benzyl; 
     or non-toxic salt or an acid addition salt thereof possess inhibitory activity on elastase, and therefore is useful for treating pulmonary emphysema, atherosclerosis and rheumatoid arthritis and the like.

This application is a Rule 62 Continuation of our application Ser. No.07/681,364, filed Apr. 8, 1991, now abandoned which in turn is a Rule 60Division of our application Ser. No. 07/364,994, filed Jun. 12, 1989,now U.S. Pat. No. 5,017,610, granted May 21, 1991.

SUMMARY

This invention is related to the derivatives of p-substituted phenylester of pivalic acid having an inhibitory activity on elastase, of thegeneral formula: ##STR4## wherein R¹, R², R³, Y and m have same meaningas described hereinafter.

BACKGROUND

Lysosomal hydrolases of neutrophils have an important role for anorganism defense reaction against tissue damage caused by microbe orinflammation etc.

Elastase and cathepsin G, which belong to neutral serine proteinaselocally existed in azurophil granule mainly play a part in decompositionof a connective tissue.

Especially, elastase degrades elastic connective tissue by cleaving thecross-linking of elastin which directly maintains the elasticity of lungtissue etc., and by cleaving hydrophobic part of protein [J. Cell.Biol., 40, 366 (1969)] and degrades the cross-linking area of collagenselectively as well as elastin [J. Biochem., 84, 559 (1978], and it actson tissue proteins such as proteoglycans etc. [J. Clin. Invest., 57,615(1976)]. Therefore, elastase plays an important role in metabolism ofconnective tissue.

Elastase is inactivated by α₁ -proteinase inhibitor (α₁ -PI) that is acommon inhibitor for serine, protetnase in vivo and the unbalance ofenzyme and inhibitor system causes the destruction of the tissue[Schweiz. Med. Wshr., 114, 895 (1984)].

The turnover of elastin in normal tissue is very slow [Endocrinology,120, 92 (1978)], but the pathological acceleration in degradation ofelastin is found under various unsound state such as pulmonary emphysema[Am. Rev. Respit. Dis., 110, 254 (1974)], atherosclerosis [Lab. Invest.,22, 228 (1970) ] and rheumatoid arthritis [in Neutral Proteases of HumanPolymorphonuclear Leukocytes, Urban and Schwarzenberg, Baltimore -Munich (1978), page 390], suggesting the relationship of elastase anddiseases Infection.Inflammation.Immunity, 13, 13 (1983)].

PRIOR ARTS

Under the background as mentioned above, recent studies and developmenton elastase inhibitors have been heartily conducted, and varioussubstances inhibiting elastase have been proposed and many patentapplications have been filed.

Particularly, recently, for example, in the specification of U.S. Pat.No. 4,683,241, the compound of the general formula: ##STR5## wherein Xarepresents a group selected from carbonyl group, methylene group, oxygenatom, azo group, sulfonyl group, --CH(OH)--, ##STR6## together with thebenzene rings represents the group ##STR7## R^(a) and R^(1a) eachrepresents an alkyl group and an acylaminoalkyl group of 2 to 6 carbonatoms, an alkoxy group, an alkenyl group and carboxyalkyl group of up to6 carbon atoms, cycloalkyl group of 3 to 6 carbon atoms or analkoxycarbonylalkyl group of up to 10 carbon atom(s), R^(2a) and R^(3a)represent hydroxy atom, halogen atom, pyranyloxy, an alkyl, an alkenyl,hydroxyalkyl and formylalkyl group of up to 4 carbon atom(s) orcarboxyalkyl group of up to 6 carbon atom(s), was disclosed.

PURPOSE OF THE INVENTION

As the result of energetic investigations conducted in order to find newelastase inhibitory agents having quite different chemical structurefrom conventional ones, tile present inventors have found that thecompound of the general formula (I) achieves this purpose.

COMPARISON WITH THE PRIOR ARTS

In the specification of U.S. Pat. No. 4,683,241, benzoylphenyl ester andbenzenesulfonylphenyl ester of any kind pivalic acid were disclosed asthe inhibitory agent on elastase.

The structure of sulfamoylphenyl ester and carbamoylphenyl ester in thepresent invention can not be obvious from compounds of the Prior Art,and it have been unexpected that compounds of the present invention haveinhibitory effect on elastase.

DISCLOSURE OF THE INVENTION

Accordingly, the present invention relates to the compounds of thegeneral formula: ##STR8## wherein Y represents sulfonyl (--SO₂ --) groupor carbonyl ##STR9## group, (i) R¹ and R², which may be the same ordifferent, each represent

(1) hydrogen atom,

(2) an alkyl group of up to 16 carbon atom(s) or an alkyl group of up to16 carbon atom(s) substituted by carboxy group

(3) a group of the formula: --X--(R⁴)n wherein

X represents single-bond, sulfonyl (--SO₂) group, an alkylene group ofup to 4 carbon atom(s) or an alkylene group of up to 4 carbon atom(s)substituted by --COOH group or benzyloxycarbonyl ##STR10## group,Arepresents carbocyclic ring or heterocyclic ring,

n represents an integer of 1 to 5,

R4 represents, same or different,

1 hydrogen atom or an alkyl group of up to 8 carbon atom(s),

2 an alkoxy group of up to 14 carbon atom(s),

3 an alkylthio group of up to 6 carbon atom(s),

4 hydroxy group, halogen atom, nitro group or trihalomethyl group,

5 a group of the formula: --NR⁴¹ R⁴² wherein R⁴ and R⁴² each represents,same or different, hydrogen atom or alkyl group of up to 4 carbonatom(s),

6 tetrazole group,

7 sulfonic acid (--SO₃ H) group or hydroxymethyl (--CH₂ OH) group,

8 a group of the formula --SO₂ NR⁴¹ R⁴² wherein R⁴¹ and R⁴² have thesame meaning as described hereinbefore,

9 a group of the formula: --Z⁴¹ --COOR⁴³ wherein

Z⁴¹ represents single-bond, an alkylene group of up to 4 carbon atom(s)or an alkenylene group of from 2 to 4 carbon atoms,

R⁴³ represents hydrogen atom, an alkyl group of up to 4 carbon atom(s)or benzyl group,

○10 a group of the formula: --CONR⁴¹ R⁴² wherein R⁴¹ and R⁴² have samemeaning as described hereinbefore,

○11 a group of the formula: --COO--Z⁴² COOR⁴³ wherein

Z⁴² represents an alkylene group of up to 4 carbon atom(s),

R⁴³ represents hydrogen atom, an alkyl group of up to 4 carbon atom(s)or benzyl group,

○12 a group of the formula: --COO--Z⁴² --CONR⁴¹ R⁴² wherein Z⁴², R⁴¹ andR⁴² have same meaning as described hereinbefore,

○13 a group of the formula: --OCO--R⁴⁵ wherein R⁴⁵ represents an alkylgroup of up to 8 carbon atom(s) or p-guantdinophenyl group,

○14 a group of the formula: --CO--R⁴⁶ wherein R⁴⁶ represents an alkylgroup of up to 4 carbon atom(s),

○15 a group of the formula: --O--Z⁴³ --COOR⁴⁵⁰ wherein

Z⁴³ represents an alkylene group of up to 6 carbon atom(s),

R⁴⁵⁰ represents a hydrogen atom, an alkyl group of up to 8 orp-guanidinophenyl group,

○16 a group of the formula: ##STR11## represents an amino acid residue,R⁴⁸ represents hydrogen atom or alkyl group of up to 4 carbon atom(s),and R⁴⁹ represents hydroxy group, alkoxy group of up to 4 carbonatom(s), amino group, amino group substituted by one or two alkyl groupof up to 4 carbon atom(s), carbamoylmethoxy or carbamoylmethoxy groupsubstituted by one or two alkyl group of up to 4 carbon atoms atnitrogen atom of carbamoyl group, R⁴⁷ represents single-bond or alkylgroup of up to 4 carbon atom(s), or wherein ##STR12## representsheterocyclic ring containing 3 to 6 carbon atoms and R⁴⁷ and R⁴⁹ haseach same meaning as described hereinbefore,

(ii) R¹, R² and nitrogen atom bonded to R¹ and R² together representsheterocyclic ring containing at least one nitrogen atom(s) andsubstituted by --COOH, or unsubstituted heterocyclic ring containing atleast one nitrogen atom(s),

R³ represents

(1) hydrogen atom,

(2) hydroxy atom,

(3) an alkyl group of up to 6 carbon atom(s),

(4) halogen atom,

(5) an alkoxy group or up to 4 carbon atom(s) or

(6) an acyloxy group of 2 to 5 carbon atoms,

m represents an integer of up to 4,

or non-toxic salts or acid addition salts thereof or process for thepreparation thereof, or inhibitory agents of elastase containing them asactive ingredient.

In this specification and claims, the term "alkyl group", "alkylenegroup", "alkenylene group", "alkoxy group" and "acyloxy group" means thestraight- or branched- chained alkyl group, alkylene group, alkenylenegroup, alkoxy group and acyloxy group.

In tile general formula (I), sulfonyl and carbonyl group represented byY are preferred.

In the general formula (I), as an alkyl group of up to 6 carbon atom(s)represented by R³, methyl, ethyl, propyl, butyl, pentyl and hexyl groupand the isomer thereof are cited, and all of them are preferred.

In the general formula (I), examples of the halogen atom, represented byR³ and R⁴ are, a fluorine atom, a chlorine atom, a bromine atom and aniodine.

In the general formula (I), examples of an alkoxy group of up to 4carbon atom(s) represented by R³, include methoxy, ethoxy, propoxy andbutyloxy group and the isomer thereof, and all of them are preferred.

In the general Formula (I), examples of an acyloxy group of 2 to 5carbon atom(s) represented by R³, include acetoxy, propionyloxy,butyryloxy and valeryloxy group and the isomer thereof are cited, andall of them are preferred.

In the general formula (I), examples of an alkyl group of up to 16carbon atom(s) represented by R¹ and R², include methyl, ethyl, propyl,butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl,tridecyl, tetradecyl, pentadecyl and hexadecyl group and the isomerthereof, and all of them are preferred.

In the general Formula (I), examples of an alkylene group of up to 4carbon atom(s) represented by X and Z⁴¹, include methylene, ethylene,trimethylene and tetramethylene group and the isomer thereof, and all ofthem are preferred.

In the general Formula (I), carbocyclic ring represented by A meansmono- or bi-aromatic carbocyclic ring(s) containing not more than 12carbon atoms which may be partially or fully saturated rings thereof.

Examples of these rings mentioned above are benzene, naphthalene,indene, azulene rings and partially or fully saturated rings thereof.

In the general formula (I), heterocyclic ring represented by Ameans-mono-, bi-aromatic heterocyclic ring(s) containing not more than12 carbon and hereto atoms which may be partially or fully saturatedrings thereof. In above heterocyclic rings, rings containing one or twoof hetero atom(s) are preferred.

Examples of these rings mentioned above are furan, thiophene, pyrrole,oxzole, isoxazole, thiazole, isothiazole, imidazole, pyrazole, furazane,pyran, pyridine, pyridazine, pyrimidine, pyrazine, indole, isoindole,benzofuran, benzothiophen, indoliine, chromen, quinoline, isoquinoline,quinolidine, purine, indazole, quinazoline, cinnoline, quinoxaline,phthalazin, pteridine rings and partially or fully saturated ringsthereof.

In the general formula (I), examples of an alkyl group of up to 8 carbonatom(s) represented by R⁴, include methyl, ethyl, propyl, butyl, pentyl,hexyl, heptyl and octyl and the isomer thereof are cited, arid all ofthem are preferred.

In the general formula (I), examples of an alkoxy group of up to 14carbon atom(s) represented by R⁴, include methoxy, ethoxy, propoxy,butoxy, pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, decyloxy,undecyloxy, dodecyloxy, tridecyloxy and tetradecyloxy group and theisomer thereof, and all of them are preferred, but particularlypreferred are methoxy, pentyloxy, decyloxy and the isomer thereof.

In the general formula (I), examples of an alkylthio group of up to 6carbon atom(s) represented by R⁴, include methylthio, ethylthio,propylthto, butylthio, pentylthio and hexylthio group and the isomerthereof, and all of them are preferred.

In the general formula (I), as R⁴, halogen, trihalomethyl, nitro,hydroxy, tetrazole, sulfonic acid and hydroxymethyl are particularlypreferred.

In the general formula (I), examples of an alkyl group of up to 4 carbonatom(s) represented by R⁴¹, R⁴², R⁴³ and R⁴⁶, include methyl ethyl,propyl and butyl group and the isomer thereof, and all of them arepreferred.

In the general formula (I), examples of an alkenylene group of 2 to 4carbon atom(s) represented by Z⁴¹, include vinylene, propenylene andbutenylene group and the isomer thereof, and all of them are preferred.

In the general formula (I), examples of an alkyl group of up to 8 carbonatom(s) represented by R⁴⁵, include methyl, ethyl, propyl, butyl,pentyl, hexyl, heptyl and octyl group and the isomer thereof, and all ofthem are preferred.

In the general formula (I), examples of an alkylene group of up to 6carbon atom(s) represented by Z⁴³, include methylene, ethylene,trimethylene, tetramethylene, pentamethylene and hexamethylene group andthe isomer thereof, and all of them are preferred.

In the general formula (I), an amino acid -residue represented byformula: ##STR13## represents every amino acid-residue, and theseresidues contain that carboxy group was converted into ester.

Preferable amino acid-residue is neutral, acidic or basic aminoacid-residue. Examples of the residues mentioned above include glycine,alanine, β-alanine, valine, phenylalanine, lysine, methionine, tyrosine,proline, leucine, tryptophan, 4-amino butyric acid, 6-aminocaproic acid,1-amino-1-phenylacetic acid, 2-amino-2phenylpropionic acid,m-aminobenzoic acid, p-aminobenzoic acid.

Examples of an alkyl group of up to 4 carbon atom(s) represented by R⁴⁸,include methyl, ethyl, propyl and butyl group and the isomer thereof.Included as exemplary of an alkyl, in alkoxy group represented by R⁴⁹,in substituent of amino group and in substituent of carbamoylmethoxygroup, methyl, ethyl, propyl and butyl group and the isomer thereof.Exemplary of the heterocyclic ring represented by ##STR14## areazetidine pyrrolidine, piperidine and perhydroazepine.

In the general formula (I), the heterocyclic ring represented by R¹, R²and the nitrogen atom bonded to R¹ and R² together, means a mono-heterocyclic ring containing 3 to 6 carbon atoms and 1 or 2 of nitrogenand/or oxygen atom(s).

Examples of these rings mentioned above are pyrrole, imidazole,pyrazole, pyrroline, pyrrolidine, imidazoline, imidazoline, pyrazoline,pyrazolidine, piperidine, piperazine, morpholine, azetidine.

An acid addition salts of the compound of the general formula (I) arepreferred non-toxic and water-soluble salts.

Suitable acid addition salts include, for example, an inorganic acidaddition salt such as hydrochloride, hydrobromide, hydroiodide, sulfate,phosphate, nitrate, or an organic acid addition salt such as acetate,lactate, tartrate, benzoate, citrate, methanesulfonate, ethanesulfonate,benzenesulfonate, toluenesulfonate, isethionate, glucuronate, gluconate.

The compounds of the present invention of the general formula (I) may beconverted into the corresponding salts by known methods. Non-toxic andwater-soluble salts are preferable. Suitable salts, for example, are asfollows: salts of alkaline metal (sodium, potassium etc.), salts ofalkaline earth metal (carcium, magnesium etc.), ammonium salts, salts ofpharmaceutically acceptable organic amine (tetramethylammonium,triethylamine, methylamine, dimethylamine, cyclopentylamine,benzylamine, phenethylamine, piperidineamine, monoethanolamine,diethanolamine, tris (hydroxymethyl)amine, lysine, arginine,N-methyl-D-glucamine etc.)

PROCESS FOR THE PREPARATION

According to the present invention, the compounds of the presentinvention of the general formula (I) may be prepared by any stepdescribed hereinafter.

In each formula,

R¹¹ and R²¹ have same meaning as that of R¹ and R², respectivelyprovided that at least either R¹¹ or R¹² represents benzyloxycarbonylgroup,

R¹² and R²² have same meaning as that of R¹ and R², respectivelyprovided that at least either R¹² or R²² represents carboxyl group,

R¹³ has same meaning that of R¹ or R² other than hydrogen atom,

R¹⁴ represents an alkyl group of up to 4 carbon atom(s), X representshalogen atom,

R³¹ represents an acyloxy group. ##STR15##

Step 1, which is an esterification reaction, conducted in the presenceof a dehydrohalogenation agent in inert organic solvents (for example,methylene chloride, ethyl acetate, benzene, hexane, diethylether), maybe carried out by reacting with corresponding pivaloyl halide under roomtemperature.

As for the dehydrohalogenation agent, there can be used a tertiaryorganic amine, or if desired, there can be used a inorganic base such asa metal bicarbonate, etc.

As a tertiary organic amine, there can be used aliphatic, aromatic orheterocyclic amine, for example, triethylamine, tributylamine,dimethylaniline, pyridine and the like.

Particularly, pyridine is preferable because it is useful also as asolvent of reaction ingredient.

Step 2, which is reaction forming the amide-bond, may be carried out byreacting the compound of the general formula (III) with correspondingamine in inert organic solvent (for example methylene chloride), in thepresence of organic or inorganic base (for example, tertiary amine suchas triethylamine), at a temperature of -20° C.˜0° C. (preferably undercooling with ice).

Step 3, which is reaction for removing a benzyl group, may be carriedout under an atmosphere of hydrogen gas, using palladium-carbon ascatalyst in a mixture of inert organic solvent (for example acetic acid,THF), at a temperature of 0° C. to 40° C.

Step 4, which is N-alkylation reaction, may be carried out reacting withalkyl halide in suitable inert organic solvent (for example, benzene,tetrahydrofuran, dimethylformamide), in the presence of a suitable base(for example, sodium hydride), at from about room temeprature to refluxtemperature.

Step 5, which is reaction for eliminating the acyl group, may be carriedout for example, in methanol, tn the precense of a catalyst (forexample, triethylamine), at or about room temperature.

The compounds of the general formula (II) and (III) used in the stephereinbefore may be prepared by combining known methods, for exampleaccording to scheme A hereinafter.

In the formula, G represents methoxy group or acetoxy group, and theother symbols have same meaning as described hereinbefore. ##STR16##

All reactions in the above schemes may be carried out by known methods.

In each reaction in the present specification, products may be purifiedby conventional manner. For example, purification may be carried out bydistillation at atomospheric or reduced pressure, high performanceliquid chromatography, thin layer chromatography or columnchromatography using silica gel or magnesium silicate, washing orrecrystallizatton. Purification may be carried out after each reaction,or after a series of reactions.

STARTING MATERIALS

The starting materials of formula (IV), (V) and (VII) in Scheme A areknown compounds, or may be easily prepared by known methods.

For example, where R¹ and R² in the formula (IV) each represents R¹ and(3)- 16 of R² in the formula (I) mentioned above, those may be preparedaccording to scheme B described hereinafter.

In the formula, the sum of p and r represents an integer of 1 to 5, andr does not represent zero.

R²⁴ has same meaning that of R⁴ other than (3) - 16 . ##STR17##

EFFECT

Derivatives of p-substituted phenyl ester of pivalic acid of the generalformula (I) of the present invention, and non-toxic acid and acidaddition salts thereof, have an inhibitory effect on elastase.

Accordingly, the derivatives of the present invention are useful fortreatment and/or prevention of diseases induced by the abnormalenhancing of the degradation of elastin, collagen fiber and/orproteoglican, by the action of elastase, in mammals, especially in humanbeings.

Examples of such diseases are pulmonary emphysema, atherosclerosis,rheumatoid arthritis and the like.

The inhibitory effects of the compounds of the invention on elastasewere confirmed by the screening system desclosed below.

INHIBITORY EFFECT ON ELASTASE (1) Method of Experiment

The test was carried out by a slight modification of the method of Biethet al [see Biochem. Med., 75, 350 (1974)] using elastase from humanneutrophil.

Namely, it is a spectrophotometric method using the synthesizedsubstrate [succinyl-alanyl-prolyl-alanyl-p-nitroanilide(Suc-Ala-Pro-Ala-pNA, produced by peptide laboratory)] which hascomparatively high specificity on neutrophil elastase.

The reaction mixture consisted of 1 mM Suc-Ala-Pro-Ala-pNA (dissolvingin N-methylpyrrolidone to the concentration of 100 mM, and then adding1/100 amount of the solution to the reaction mixture.), 0.1M buffersolution of tris-hydrochloric acid (pH 8.0), 0.2M sodium chlorideaqueous solution, the sample solution of various concentrations andenzyme solution in a final volume of 1.0 ml was incubated at 37° C. for30 minutes.

The reaction was stopped by the addition of 100 μl of 50% acetic acidinto the reaction mixture, and then p-nitro anilide released wasmeasured on absorbance of 405 nm.

Inhibition percentage of the test compounds was calculated by thefollowing equation: ##EQU1##

(2) Results

The results are shown in Table 1.

                                      TABLE I                                     __________________________________________________________________________    Inhibitory effect of elastase                                                  ##STR18##                                                                    __________________________________________________________________________         Structure                                                                 No.Example                                                                         ##STR19##                   Name                  (μM)of                                                                    elastasenhibitory                                                             effect                 __________________________________________________________________________     1                                                                                  ##STR20##                  p-[N-(p-bromophenyl)-N-methylsulfamoyl]                                       phenyl ester of pivalic                                                                             0.031                  1(2)                                                                                ##STR21##                  p-sulfamoylphenyl ester of pivalic                                                                  0.77                   1(3)                                                                                ##STR22##                  p-(N-cyclohexylsulfamoyl)phenyl ester of                                      ivalic acid           0.042                  1(8)                                                                                ##STR23##                  p-[N-(p-chlorophenyl)sulfamoyl]phenyl                                         ester of pivalic acid 0.03                   1(12)                                                                               ##STR24##                  p-[(1-imidazolyl)sulfonyl]phenyl ester                                        of pivalic acid       0.05                   1(14)                                                                               ##STR25##                  p-[N-(α-pyridyl)sulfamoyl]phenyl                                        ester of pivalic acid 0.19                   1(15)                                                                               ##STR26##                  1-acetoxy-4-[N,N-bis(p-pivaloyloxy-                                           phenylsulfonyl)amino]benzene                                                                        0.048                  2(5)                                                                                ##STR27##                  p-(N-tert-butylsulfamoyl)phenyl ester of                                      ivalic acid           0.053                  2(38)                                                                               ##STR28##                  2-methyl-4-[N-(o-(N,N- diethylcarbamoyl]m                                     ethyoxycarbonyl)phenyl) sulfamoyl]phenyl                                      ester of pivalic acid 0.072                  2(49)                                                                               ##STR29##                  2-methyl-4-[N-(1,4-dioxa-2-carboxy-8-yl-                                      aphthalene)sulfamoyl]phenyl ester of                                          pivalic acid          0.15                   2(51)                                                                               ##STR30##                  2-methyl-4-[N-(o-carboxypropoxyphenyl)                                        sulfamoyl]phenyl ester of pivalic                                                                   0.64                   2(62)                                                                               ##STR31##                  2-methyl-4-[N-(o-prolylcarbonylphenyl)                                        sulfamoyl]phenyl ester of pivalic                                                                   0.69                   2(63)                                                                               ##STR32##                  N-[O-(p-pivaloyloxybenzene) sulfonylamino                                     benzoyl]glycine       0.044                  __________________________________________________________________________         Structure                                                                 No.Example                                                                         ##STR33##                   Name                  (μM)of                                                                    elastasenhibitory                                                             effect                 __________________________________________________________________________    2(67)                                                                               ##STR34##                  N-[O-(3-methyl-4- pivaloyloxybenzene)sulf                                     onylaminobenzyoyl]- L-phenylanine                                                                   0.41                   2(68)                                                                               ##STR35##                  N-[O-(3-methyl-4-pivaloyloxybenzene)                                          sulfonylaminobenzoyl]-dl-methionine                                                                 0.20                   2(69)                                                                               ##STR36##                  N-[O-(3-methyl-4-pivaloyloxybenzene)                                          sulfonylaminobenzoyl]-L-lysine                                                hydrochloride         0.52                   2(80)                                                                               ##STR37##                  N-[5-methylthio-2-(p-pivaloyloxybenzene)                                      ulfonylaminobenzoyl]glycine                                                                         0.021                  2(87)                                                                               ##STR38##                  N-[2-(p-pivaloyloxybenzene)sulfonylamino-                                     5- propylthiobenzoyl]glycine                                                                        0.024                  4(5)                                                                                ##STR39##                  p-(N-phenetylsulfamoyl)phenyl ester of                                        pivalic acid          0.072                  5(3)                                                                                ##STR40##                  p-[N-(o-carboxyphenyl)sulfamoyl]phenyl                                        ester of pivalic acid 0.023                  __________________________________________________________________________

The result of the experiment showed that the compounds of the presentinvention have an inhibitory effect on elastase.

TOXICITY

Further, it was confirmed that the toxicity of the compounds of thepresent invention is low enough such that they can be used safely formedical supplies.

Application

Accordingly, it was confirmed that the compounds of the presentinvention can be useful for the treatment and/or prevention of diseasesinduced by abnormal enhancing of degradation of proteins such as elastinand the like, by the action of elastase in mammals, especially in humanbeings.

Administration

For the purpose mentioned above, the compounds of the present invention,described in the general formula (I) or an acid addition salts thereofmay normally be administered systemically or partially, usually by oralor parenteral administration.

The dose to be administered is determined depending upon age, bodyweight, symptom, the desired therapeutic effect, the route ofadministration, and the duration of the treatment etc. In the humanadult, the doses per person for one time are generally between 1 mg and500 mg, by oral administration up to several times per day, and between0.1 mg and 200 mg, by parenteral administration (preferably byIntravenous administration) up to several times per day.

As mentioned above, the doses to be used depend on various conditions.Therefore, there are cases in which doses lower than the rangesspecified above and doses greater than the ranges specified above, maybe used.

Solid compositions according to the present invention for oraladministration include compressed tablets, dispersible powders andgranules. In such solid compositions, one or more of the activecompound(s) is, or are, admixed with at least one inert diluent such aslactose, mannitol, glucose, hydroxypropyl cellulose, microcrystallinecellulose, starch, polyvinyl-pyrrolidone or magnesium matesilicatealuminate. The compositions may also comprise, as is normal practice,additional substances other than inert diluents e.g. lubricating agentssuch as magnesium stearate, and, disintegrating agents such as cellulosecalcium glycolate, stabilizing agents such as lactose, and solubilizerssuch as glutamic acid and asparagintc acid. The tablets or pills may, ifdesired, be made into gastric film-coated or enteric film-coated tabletsor pills, such as sugar-coated, gelatin-coated,hydroxypropylcellulose-coated or hydroxypropylmethylcellulosephthalate-coated tablets or pills; two or more layers may be used. Thecompositions For oral administration also include capsules of absorbablematerial such as gelatin.

Liquid compositions for oral administration includepharmaceutically-acceptable emulsions, solutions, suspensions, syrupsand elixirs containing inert diluents commonly used in the art such asdistilled water or ethanol. Besides inert diluents such compositions mayalso comprise adjuvants such as wetting and suspending agents, andsweetening, flavouring, perfuming and preserving agents.

Other compositions for oral administration include spray compositionswhich may be prepared by known methods and which comprise one or more ofthe active compound(s). Besides inert diluents such compositions mayalso comprise stabilizers such as sodium bisulfite and buffer forisotonicity, for example sodium chloride, sodium citrate or citric acid.

The manufacturing methods of spray compositions have been described indetail, for example, in the specifications of U.S. Pat. Nos. 2,868,691and 3,095,355.

Preparations for injection according to the present invention forparenteral administration include sterile aqueous or non-aqueoussolutions, suspensions or emulsions. Example of aqueous solvents orsuspending media are distilled water for injection and physiologicalsalt solution. Examples of non-aqueous solvents or suspending media arepropylene glycol, polyethylene glycol, vegetable oils such as olive oil,alcohols such as ethanol, Polysorbate 80 (registered Trade Mark). Thesecompositions may also include adjuvants such as preserving, wetting,emulsifying and dispersing agents stabilizing agents (e.g. lactose) andsolubilizers (e.g. glutamic acid and asparaginic acid). They may besterilized, for example, by filtration through a bacteria-retainingfilter, by incorporation of sterilizing agents in the compositions or byirradiation. They may also be manufactured in the form of sterile solidcompositions which can be dissolved in sterile water or some othersterile injectable medium immediately before use.

Other compositions for parenteral administration include liquids forexternal use, and endermic liniments such as ointments, suppositoriesfor rectal administration and passaries for vaginal administration whichcomprise one or more of the active compound(s) and may be prepared byknown methods.

EXAMPLES AND COMPARATIVE EXAMPLES

The following Reference Examples and Examples illustrate the preparationof compounds of the present invention, however, the present invention isnot restricted to them. In the Reference Examples and Examples, "TLC","NMR" and "IR" each represents "thin layer chromatography", "nuclearmagnetic resonance" and "infrared absorption spectrum", respectively.

The solvents in the parentheses show the developing or eluting solventsand the ratios of the solvents used are by volume in chromatographicseparation.

Unless otherwise specified, "IR" were measured by KBr method, and "NMR"were measured in bichloroform (CDC₃).

REFERENCE EXAMPLE 1 1- (N-methyl-N-phenyl )sulfamoyl -4-methoxybenzene##STR41##

p-methoxybenzenesulfonyl chloride (965 mg) was dissolved in the mixtureof triethylamine (2 ml), methylaniline (500 mg) and methylene chloride(10 ml) under cooling with ice, and the mixture was stirred for 30minutes.

The reaction solution was stirred overnight at room temperature. Afterthe reaction was finished, the reaction solution was extracted withether. The extract was washed successively with 1N-HCl, water and asaturated aqueous solution of sodium chloride.

The solution was dried over sodium sulfate, and distilled off underreduced pressure to give the title compounds.

REFERENCE EXAMPLE 2 p-[N-methyl-N-(p-bromophenyl)sulfamoyl]phenol##STR42##

Boron tribromide (2.2 ml) was added to the solution of methylenechloride (10 ml) of the compound obtained by Reference Example 1 undercooling with ice, and stirred for 2 hours at room temperature.

The reaction solution was allowed to cool to -20° C.˜-30° C., and waterwas added thereto, and the solution obtained was extracted with ethylacetate. The extract was washed successively with water and saturatedaqueous solution of sodium chloride.

The solution was dried over sodium sulfate, and distilled off underreduced pressure and the residue was purified by column chromatographyon silica-gel (methylene chloride: ethyl acetate=10:1) to give the titlecompound (900 mg) having the following physical data;

TLC: Rf 0.20 (methylene chloride: ethyl acetate=30:1).

REFERENCE EXAMPLE 3 p-[N-[(p-tolyl)carbamoyl]phenol ##STR43##

Potassium carbonate (500 mg) was added into methanol solution (50 ml) of[p-acetoxy-N-(p-tolyl)]benzamide (300 mg) obtained by the same procedureas Reference Example 1, and the mixture was stirred overnight.

The obtained reaction solution was distilled off under reduced pressure,and extracted with ethyl acetate. The extract was washed successivelywith 1N-hydroic acid, water and saturated aqueous solution of sodiumchloride.

The solution was dried with magnesium sulfate, and distilled off underreduced pressure to give the title compound having the followingphysical data.

TLC: Rf 0.31 (methylene chloride: ethyl acetate=10:1).

EXAMPLE 1 p-[N-(p-bromophenyl)-N-methylsulfamoyl)]phenyl ester ofpivalic acid ##STR44##

Pivaloyl chloride (0.5 ml) was added to the mixture solution oftriethylamine (1.5 ml)-methylene chloride (5 ml) of the compoundsobtained by procedure of Reference Example 2 under cooling with ice. Thereaction solution was allowed to stand for 10 minutes, and stirred forone hour at room temperature.

The reaction solution was extracted with ether, and the extract waswashed successively with water, 1N-HCl, water, saturated aqueoussolution of sodium bicarbonate, water and saturated aqueous solution ofsodium chloride. The solution was dried with sodium sulfate, anddistilled off under reduced pressure.

The concentrate was recrystallized with ethyl acetate-hexane to give thetitle compound (510 mg) having the following physical data.

TLC: Rf 0.81 (methylene chloride: ethyl acetate=30:1);

IR: 1750, 1590, 1460, 1400, 1350 cm⁻¹.

Hereinafter, the title-compound, which was described in the followingTable II and III, was given by using corresponding starting materialsand by operating the same procedure as Reference Example 1→ReferenceExample 2 (or Reference Example 3)→+Example 1.

                                      TABLE II                                    __________________________________________________________________________     ##STR45##                                                                     No.pleam-Ex-                                                                     ##STR46##            Name               TLC       or NMRIR                __________________________________________________________________________                                                         (cm.sup.-1)              1(1)                                                                              ##STR47##           p-(N-phenylsulfamoyl)phenyl ester of pivalic                                                     Rf 0.3 (hexane: ethyl acetate:                                                = 5:2)    δ 7.7(2H, d),                                                           7.3˜6.9(7H,                                                             m), 6.5(1H, 6s),                                                              1.3(9H, s)               1(2)                                                                             NH.sub.2             p-sulfamoylphenyl ester of pivalic                                                               Rf 0.72   ν 3400, 3280,                                                              1720,                                            acid               (hexane:  1580, 1480, 1350                                                    ethyl acetate:                                                                          1200, 1160, 1120                                                    1:2)                               1(3)                                                                              ##STR48##           p-(N-cyclohexylsulfamoyl)phenyl ester of pivalic                              acid               Rf 0.82  (hexane: ethyl                                                       acetate: = 1:1)                                                                         ν 3280, 2940,                                                              1750, 1590, 1480,                                                             1440, 1320, 1210,                                                             1160, 1100               1(4)                                                                              ##STR49##           p-[N-(p-tolyl)sulfamoyl]phenyl ester of pivalic                               acid               Rf 0.62 (methylene chloride:                                                  ethyl acetate:                                                                          ν 3300, 1740,                                                              1580, 1500, 1380,                                                             1330, 1270, 1200         1(5)                                                                              ##STR50##           p-[N-(p-benzyloxycarbonylphenyl) sulfamoyl]phenyl                             ester of pivalic acid                                                                            Rf 0.75 (hexane: ethyl                                                        acetate: =  1:1)                                                                        ν 1750, 1720,                                                              1600, 1460, 1340,                                                             1270, 1150, 1100         1(6)                                                                              ##STR51##           p-[N-(4-N, N-dimethylamino)phenyl) sulfamoyl]pheny                            l ester of pivalic acid                                                                          Rf 0.78 (hexane: ethyl                                                        acetate: = 1:2)                                                                         ν 1750, 1610,                                                              1590, 1520, 1330,                                                             1200, 1150, 1100         1(7)                                                                             NHC.sub.10 H.sub.21  p-(N-decylsulfamoyl)phenyl ester                                                                 Rf 0.60   ν 3300, 2930,                                                              2850,                                            pivalic acid       (methylene                                                                              1750, 1590                                                          chloride:                                                                     ethyl acetate: =                                                              30:1)                              1(8)                                                                              ##STR52##           p-[N-(4-chlorophenyl)sulfamoyl] phenyl ester of                               pivalic acid       Rf 0.52 (methylene chloride:                                                  ethyl acetate:                                                                          ν 3260, 2970,                                                              1750, 1590, 1490,                                                             1450, 1340               1(9)                                                                              ##STR53##           p-[N-(m-chlorophenyl)sulfamoyl] phenyl ester of                               pivalic acid       Rf 0.50 (methylene chloride:                                                  ethyl acetate:                                                                          ν 3250, 1750,                                                              1590, 1480, 1400,                                                             1330, 1200               1(10)                                                                             ##STR54##           p-[N-(β-pyridyl)sulfamoyl]phenyl ester of                                pivalic acid       Rf 0.50 (methylene chloride:                                                  methanol = 10:1)                                                                        ν 3600˜3200,                                                          1750, 1580, 1470,                                                            1400, 1350, 1310,                                                             1260, 1200               1(11)                                                                             ##STR55##           p-[N-(p-pentylphenyl)sulfamoyl phenyl ester of                                pivalic acid       Rf 0.46 (methylene chloride:                                                  ethyl acetate:                                                                          ν 3960, 3920,                                                              3850, 3250, 1750,                                                             1610, 1590, 1510,                                                             1480, 1460, 1400,                                                             1330 (neat)              1(12)                                                                             ##STR56##           p-[(1-imidazolyl)sulfonyl]phenyl ester of pivalic                             acid               Rf 0.52 (methylene chloride:                                                  ethyl acetate:                                                                          δ 7.96(2H, d),                                                          8.0 (1H, m),                                                                  7.28(2H, d),                                                                  7.28(1H, m),                                                                  7.09(1H, m), 1.36                                                             (9H, s)                  1(13)                                                                             ##STR57##           (p-morpholinosulfonyl)phenyl ester of pivalic                                 acid               Rf 0.19 (methylene chloride:                                                  ethyl acetate:                                                                          ν 2970, 2860,                                                              1759, 1590, 1480,                                                             1340                     1(14)                                                                             ##STR58##           p-[N-(α-pyridyl)sulfamoyl]phenyl ester of                               pivalic acid       Rf 0.64 (chloroform: methanol:                                                = 30:1)   ν 3200˜2300,                                                          1750, 1630, 1610,                                                            1520,  1490, 1480,                                                            1460, 1380, 1360         1(15)                                                                             ##STR59##           1-methoxy-4-[N, N-bis(p- pivaloyloxyphenylsulfonyl                            ) amino]benzene    Rf 0.61 (methylene chloride:                                                  ethyl acetate                                                                           ν 3400, 2970,                                                              1750, 1590,              __________________________________________________________________________                                                         1480                 

                                      TABLE III                                   __________________________________________________________________________     ##STR60##                                                                     No.Example                                                                         ##STR61##    Name              TLC       or NMRIR                       __________________________________________________________________________                                                  (cm.sup.-1)                     1(16)                                                                               ##STR62##   p-[N-(p-tolyl)carbamoyl]phenyl ester of pivalic                                                 Rf 0.46 (methylene chloride: ethyl                                            chloride: = 30:1)                                                                       ν 3300, 2960, 1740,                                                        1640, 1600,                     __________________________________________________________________________                                                  1500                        

REFERENCE EXAMPLE 4 sodium salt of p-pivaloyloxybenzenesulfonic acid##STR63##

Pivaloyl chloride (2.4 g) was dissolved in the mixture of 4N-aqueoussolution of sodium hydroxide (7.5 ml) of phenol 4-sulfonic acid (1.74 g)and tetrahydrofuran (5 ml), and the mixture was stirred for 10 minutesunder cooling with ice. The mixture was reacted for one hour at roomtemperature.

The reaction on solution was distilled off under reduced pressure, andthe crystal was filtered off.

The obtained crystal was washed twice with a small amount of ice-water,and dried to give the title compound (1.26 g) having the followingphysical data.

TLC: Rf 0.65 (ethyl acetate: acetic acid: water=6:2:1).

REFERENCE EXAMPLE 5 p-pivaloyloxybenzenesulfonyl chloride ##STR64##

Thionyl chloride (2.1 ml) was added to dimethylformamide solution (33ml) of tile compound (2.8 g) of Reference Example 4, and the mixture wasstirred for 30 minutes under cooling with ice, and stirred for 30minutes at room temperature.

The reaction solution was extracted with ether-hexane (1:1), and theextract was washed twice with ice-water.

The solution was dried with magnesium sulfate to give the title compound(2.49 g) having the Following physical data.

TLC: Rf 0.34 (hexane:ethyl acetate=10: 1).

EXAMPLE 2 [N-((trans-p-carboxycyclohexyl)methyl)sulfamoyl]phenyl esterof pivalic acid ##STR65##

By using sulfonyl chloride of Reference Example 5, and by the sameprocedure of Reference Example 1, the title compound (110 mg) havingtile following physical data was obtained.

TLC: RF 0. 32 (chloroform:methanol:acetic acid=100:5:1);

NMR: 7.9(2 H,d), 7.25(2 H,d), 4.4(1 H,m), 2.8(2 H,m), 2.4˜1.0(9 H,m),1.35(9 H,s).

Hereinafter by using sulfonyl chloride of Reference Example 5 andcorresponding amine, and by the same procedure of Example 2, the desiredcompounds described in the Following Table IV and V were obtained.

                                      TABLE IV                                    __________________________________________________________________________     ##STR66##                                                                     No.ampleEx-                                                                       ##STR67##            Name                TLC     or NMRIR                __________________________________________________________________________                                                         (cm.sup.-1)              2(1)                                                                              ##STR68##           p-[N-(p-carboxymethylphenyl) sulfamoyl]phenyl                                 ester of pivalic acid                                                                             Rf 0.3 (chloroform: methanol:                                                 cetic acid = 100:5:1)                                                                 (CDCl.sub.3 +                                                                 CD.sub.3 OD): δ                                                         .8(2H,                                                                        d), 7.4˜7.0(6H,                                                         m), 3.55(2H, s),                                                              1.35(9H, s)               2(2)                                                                              ##STR69##           p-[N-(p-(trans-2-carboxyvinyl) phenyl)sulfamoyl]ph                            enyl ester of pivalic acid                                                                        Rf 0.33 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD): δ                                                         .0˜7.0(10H, m),                                                         .2(1H, d), 1.35(9H,                                                           s)                        2(3)                                                                              ##STR70##           p-[N-(m-carboxyphenyl)sulfamoyl] phenyl ester of                              pivalic acid        Rf 0.31 (chloroform: methanol:                                                 acetic acid                                                                          CDCl.sub.3 + CD.sub.3                                                         OD): δ 7.85(2H,                                                         d), 7.8˜7.65(2H,                                                         m), 7.5˜7.3(3H,                                                         m), 7.2˜7.0(2H,                                                         d)                       2(4)                                                                              ##STR71##           p-[N-(p-carboxybenzyl)sulfamoyl] phenyl ester of                              pivalic acid        Rf 0.31 (chloroform: methanol:                                                 acetic acid                                                                          δ 8.1˜7.8(                                                        4H,                                                                           m), 7.5˜7.2(5H,                                                         m), 4.2(2H, s),                                                               1.35(9H, s)               2(5)                                                                             NHC(CH.sub.3).sub.3  p-(N-tert-butylsulfamoyl)phenyl                                                                   Rf 0.65 ν 3260, 2980,                                                              1740,                        H                    of pivalic acid     (methylene                                                                            1590, 1480, 1310,                                                     chloride:                                                                             1200                                                                  ethyl acetate =                                                               30:1)                             2(6)                                                                              ##STR72##           p-[N-(p-acetoxyphenyl)sulfamoyl] phenyl ester of                              pivalic acid        Rf 0.58 (ethyl acetate:                                                       hexane = 1:1)                                                                         ν 3260, 2960,                                                              1750, 1740, 1590,                                                             1300, 1470, 1400,                                                             1340, 1230, 1190,                                                             1150, 1100                2(7)                                                                              ##STR73##           p-[N-(p-hydroxyphenyl)sulfamoyl] phenyl ester of                              pivalic acid        Rf 0.08 (methylene chloride:                                                  ethyl acetate                                                                         ν 1745, 1590,                                                              1510, 1400, 1320,                                                             1270, 1200                2(8)                                                                              ##STR74##           p-[N-(m-hydroxyphenyl)sulfamoyl] phenyl ester of                              pivalic acid        Rf 0.10 (methylene chloride:                                                  ethyl acetate                                                                         ν  3400, 3240,                                                             1640, 1610, 1600,                                                             1480                      2(9)                                                                              ##STR75##           p-[N-(4-pyridyl)sulfamoyl]phenyl ester of pivalic                             acid                Rf 0.30 (chloroform: methanol                                                 = 10:1) ν 3500˜2300,                                                         1750, 1630, 1590,                                                             1490, 1350                2(10)                                                                             ##STR76##           p-[N-(p-sulfamoylphenyl)sulfamoyl] phenyl ester                               of pivalic acid     Rf 0.18 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD): δ                                                         .9(2H, d), 7.75 (2H,                                                          d), 7.3(2H, d),                                                               7.2(2H, d), 1.35(9H,                                                          s)                        2(11)                                                                             ##STR77##           p-[N-(p-carbamoylphenyl)sulfamoyl] phenyl ester                               of pivalic acid     Rf 0.22 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD): δ                                                         .85(2H, d),  7.70(2H,                                                         d) 7.18(2H, d),                                                               7.14(2H, d)               2(12)                                                                             ##STR78##           p-[N-(α-pyridylmethyl)sulfamoyl] phenyl                                 ester of pivalic acid                                                                             Rf 0.75 (chloroform: methanol:                                                 = 10:1)                                                                              ν 1750, 1590,                                                              1480, 1330, 1200,                                                             1160                      2(13)                                                                             ##STR79##           p-[N-(β-pyridylmethyl)sulfamoyl] phenyl                                  ester of pivalic acid                                                                             Rf 0.57 (chloroform: methanol:                                                 = 10:1)                                                                              ν 1750, 1590,                                                              1480, 1320, 1200,                                                             1150, 1100                2(14)                                                                             ##STR80##           p-[N-(4-pyridylmethyl)sulfamoyl] phenyl ester of                              pivalic acid        Rf 0.57 (chloroform: methanol:                                                 = 10:1)                                                                              ν 1750, 1600,                                                              1590, 1480, 1420,                                                             1320, 1200                2(15)                                                                             ##STR81##           p-[N-(o-hydroxyphenyl)sulfamoyl] phenyl ester of                              pivalic acid         Rf 0.42 (methylene chloride:                                                 thyl acetate                                                                          ν 3450, 3250,                                                              1730, 1590, 1480,                                                             1430                      2(16)                                                                             ##STR82##           P-[(3-carboxy)piperidinosulfonyl] phenyl ester of                             pivalic acid        Rf 0.41 (chloroform: methanol:                                                 acetic acid                                                                          δ 7.8(2H, d),                                                           7.3(2H,                                                                       d), 4.0˜3.4(3H,                                                         b), 3.0˜1.3(6H,                                                         b), 1.35(9H, s)           2(17)                                                                             ##STR83##           2-methyl-4-(N-phenylsulfamoyl) phenyl ester of                                pivalic acid        Rf 0.44 (hexane: ethyl                                                        acetate = 5:2)                                                                        δ 7.7˜7.5(                                                        2H,                                                                           m), 7.4˜7.0(6H,                                                         m), 6.45(1H, bs),                                                             2.2(3H, s), 1.35(9H,                                                          s)                        2(18)                                                                             ##STR84##           2-methyl-4-[N-methyl-N-(o-carboxy) sulfamoyl]pheny                            l ester of pivalic acid                                                                           Rf 0.43 (chloroform: methanol:                                                 acetic acid                                                                          δ 7.9 (1H, dd),                                                         .7˜7.0(6H, m),                                                          3.35(3H, s),  2.2(3H,                                                         s), 1.4(9H, s)            2(19)                                                                             ##STR85##           2-methyl-4-[(2S-carboxy-1- pyrolidinyl)sulfonyl]ph                            enyl ester of pivalic acid                                                                        Rf 0.26 (chloroform: methanol:                                                 acetic acid                                                                          δ 7.8(1H, s),                                                           7.75 (1H, d), 7.2(1H,                                                         ), 4.4˜4.2(1H,                                                          m), 2.4˜1.6(7H,                                                         ), 1.4(9H, m)             2(20)                                                                             ##STR86##           2-methyl-4-[N-(p- carboxycyclohexanemethyl)sulfamo                            yl] phenyl ester of pivalic acid                                                                  Rf 0.40 (chloroform: methanol:                                                 acetic acid                                                                          δ 7.8(1H, s),                                                           7.75(1H, d), 2.85(2H,                                                         d), 2.3(3H, s),                                                               1.4(9H, s)                2(21)                                                                             ##STR87##           2-methyl-4-[(4-carboxy) piperidinosulfonyl]phenyl                             ester of pivalic acid                                                                             Rf 0.36 (chloroform: methanol:                                                 acetic acid                                                                          δ 7.65(1H, s),                                                          7.6 (1H, d),                                                                  3.8˜3.4 (3H,                                                            b), 2.7˜2.3                                                             (2H, m), 2.25(3H, s),                                                         2.2˜1.6(5H, b),                                                         1.4(9H, s)                2(22)                                                                             ##STR88##           2-methyl-4-[(3-carboxy) piperidinosulfonyl]phenyl                             ester of pivalic acid                                                                             Rf 0.36 (chloroform: methanol:                                                 acetic acid                                                                          δ 7.68(1H, s),                                                          7.61 1H, d),                                                                  3.9˜3.3 (2H,                                                            m), 2.8˜2.4                                                             (3H, m), 2.25(3H, s),                                                         1.35(9H, s)               2(23)                                                                             ##STR89##           2-methyl-4-[(N-((o-methoxycarbonyl) phenyl)sulfamo                            yl]phenyl ester of pivalic acid                                                                   Rf 0.6 (methylene chloride:                                                   ethyl acetate                                                                         ν 3125, 2970,                                                              1740, 1685, 1600,                                                             1580, 1490, 1265,                                                             1110, 940, 760            2(24)                                                                             ##STR90##           2-methyl-4-[N-((o-acetyl)phenyl) sulfamoyl]phenyl                             ester of pivalic acid                                                                             Rf 0.6 (methylene chloride:                                                   ethyl acetate                                                                         ν 2980, 1755,                                                              1640, 1605, 1580,                                                             1495, 1450, 1400,                                                             1260, 1150, 1105          2(25)                                                                             ##STR91##           2-methyl-4-[N-((o-aminocarbonyl) phenyl)sulfamoyl]                            phenyl ester of pivalic acid                                                                      Rf 0.1 (methylene chloride:                                                   ethyl acetate                                                                         ν 3450, 3200,                                                              2970, 1730, 1670,                                                             1615, 1575, 1490,                                                             1340, 1280, 1220,                                                             1150, 1110                2(26)                                                                             ##STR92##           2-methyl-4-[(2-carboxy) piperidinosulfonyl]phenyl                             ester of pivalic acid                                                                             Rf 0.41 (chloroform: methanol:                                                 acetic acid                                                                          δ 7.7(1H, d),                                                           7.75 (1H, s), 7.1(1H,                                                         ), 4.8(1H, b), 3.8                                                            (1H, b), 3.2(1H, b),                                                          2.2(3H,                                                                       s), 2˜1.2(6H,                                                           b), 1.35(9H, s)           2(27)                                                                             ##STR93##           2-methyl-4-[N-(o-phenyl)sulfamoyl] phenyl ester                               of pivalic acid     Rf 0.20 (hexane: ethyl                                                        acetate = 5:2)                                                                        δ 7.5(2H, b),                                                           7.2˜6.5(5H, m),                                                         .2(2H, b), 2.1(3H,                                                            s), 1.3(9H, s)            2(28)                                                                             ##STR94##           2-methyl-4-[N-(o-N,N-dimethyl- carbamoylmethoxycar                            bonyl)phenyl)sulfa moyl]phenyl ester of pivalic                               acid                Rf 0.51 (chloroform: methanol:                                                 acetic acid                                                                          ν 1760, 1690,                                                              1680, 1490, 1590,                                                             1410, 1260, 1150,                                                             1110                      2(29)                                                                            NH(CH.sub.2).sub.2 COOH                                                                            2-methyl-4-[(N-carboxyethyl)                                                                      Rf 0.33 (CDCl.sub.3)                 2-CH.sub.3           sulfamoyl]phenyl ester of pivalic                                                                 (chloroform:                                                                          δ 7.8(1H, s),                                                           7.75                                              acid                methanol:                                                                             (1H, d), 7.15(1H,                                                     acetic acid                                                                           d), 5.7(1H, b),                                                       100:5:1)                                                                              3.25(2H, m), 2.6                                                              (2H, t), 2.25(3H,                                                             s), 1.35(9H, s)           2(30)                                                                             ##STR95##           2-methyl-4-[N-(o-carboxycyclo-pentyl) sulfamoyl]ph                            enyl ester of pivalic acid                                                                        Rf 0.33 (Chloroform: methanol                                                 = 10:1) (CDCl.sub.3) δ                                                          7.8(1H, s), 7.75 (1H,                                                         d), 7.12(1H, d),                                                              4.0˜3.6(1H, b),                                                         2.25(3H,                                                                      s), 2.1˜1.6(6H,                                                         b), 1.35(9H, s)           2(31)                                                                             ##STR96##           2-methyl-4-[N-(o-carboxycyclo-hexyl) sulfamoyl]phe                            nyl ester of pivalic acid                                                                         Rf 0.33 (chloroform methanol:                                                 = 10:1) (CDCl.sub.3) δ                                                          7.65˜7.90(2H,                                                           m), 7.1(1H, d),                                                               2.25(3H, s), 1.4(9H,                                                          s), 1.0˜3.0(10H,                                                         m)                       2(32)                                                                             ##STR97##           2-methyl-4-[N-(2-methoxy-5-carboxy) sulfamoyl]phen                            yl ester of pivalic acid                                                                          Rf 0.33 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          8.18(1H, d), 7.8 (1H,                                                         d, d), 7.6(1H, s),                                                            7.53(1H, d), 6.95(1H,                                                         d), 6.75 (1H, d),                                                             3.65(3H, s), 2.2(3H,                                                          s), 1.35(9H, s)           2(33)                                                                             ##STR98##           2.6-dimethyl-4-[N-(p-tolyl)sulfamoyl] phenyl                                  ester of pivalic acid                                                                             Rf 0.44 (methylene chloride:                                                  ethyl acetate                                                                         ν 1750, 1470,                                                              1390, 1330, 1280,                                                             1140, 1100                2(34)                                                                             ##STR99##           4-[N-(o-hydroxymethylphenyl) sulfamoyl]phenyl                                 ester of pivalic acid                                                                             Rf 0.76 (ethyl acetate:                                                       hexane = 2:1)                                                                         ν 3470, 3050,                                                              2950, 2850, 1750,                                                             1590, 1470, 1320,                                                             1210                      2(35)                                                                             ##STR100##          2-methyl-4-[N-trans-o-carboxy- cylcopentyl)sulfamo                            yl]phenyl ester of pivalic acid                                                                   Rf 0.33 (chloroform: methanol:                                                 = 10:1)                                                                              (CDCl.sub.3) δ                                                          7.75(1H, s), 7.7 (1H,                                                         d), 7.1(1H, d),                                                               3.75(1H, m), 2.5(1H,                                                          m), 2.25 (3H, s),                                                             2.4˜1.4 (6H,                                                            m), 1.4(9H, s)            2(36)                                                                             ##STR101##          2-methyl-4-[N-(cis-o-carboxyl- cyclopentyl)sulfamo                            yl]phenyl ester of pivalic acid                                                                   Rf 0.33 (chloroform:                                                          methanol = 10:1)                                                                      (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.75(1H, s), 7.7 (1H,                                                         d), 7.1(1H, d),                                                               3.75(1H, m), 2.8(1H,                                                          m), 2.25 (3H, s),                                                             2.0˜1.4 (6H,                                                            m), 1.4(9H, s)            2(37)                                                                             ##STR102##          2-methyl-4-[N-cis-o-carboxy- cyclohexyl)sulfamoyl]                            phenyl ester of pivalic acid                                                                      Rf 0.18 (chloroform: methanol:                                                 = 10:1)                                                                              ν 3260,                                                                    2400˜2700,                                                              1740, 1700, 1470,                                                             1420, 1330                2(38)                                                                             ##STR103##          2-methyl-4-[N-(o-(N,N-diethyl- carbamoylmethoxycar                            bonyl)phehyl) sulfamoyl]phenyl ester of pivalic                               acid                Rf 0.55 (methylene chloride:                                                  ethyl acetate                                                                         ν 3160, 3000,                                                              1755, 1670, 1590,                                                             1490, 1270, 1100,                                                             940                       2(39)                                                                             ##STR104##          2-methyl-4-[N-(o-sulfamoylphenyl) sulfamoyl]phenyl                             ester of pivalic acid                                                                            Rf 0.20 (chloroform: methanol:                                                 acetic acid                                                                          ν 1750, 1720,                                                              1590, 1570, 1460          2(40)                                                                             ##STR105##          2-methyl-4-[N-(m-carboxyphenyl) sulfamoyl]phenyl                              ester of pivalic acid                                                                             Rf 0.33 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.75˜7.4(3H,                                                            m), 7.4˜7.1(3H,                                                         m), 6.97(1H, d),                                                              2.15(3H, s), 1.35(9H,                                                         s)                        2(41)                                                                             ##STR106##          4-[N-(m-carboxymethylphenyl) sulfamoyl]phenyl                                 ester of pivalic acid                                                                             Rf 0.33 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.7(2H,                                                                       d), 7.2˜6.8(6H,                                                         m), 3.45(2H, s),                                                              1.30(9H, s)               2(42)                                                                             ##STR107##          2-methyl-4-[N-(m-carboxymethyl- phenyl)sulfamoyl]p                            henyl ester of pivalic acid                                                                       Rf 0.31 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.55(1H, s), 7.5(1H,                                                          d), 7.2˜6.8(5H,                                                         m), 3.45(2H, s),                                                              2.15(3H, s), 1.35(9H,                                                         s)                        2(43)                                                                             ##STR108##          2-methyl-4-[N-(m-carboxyethylphenyl) sulfamoyl]phe                            nyl ester of pivalic acid                                                                         Rf 0.31 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          7.62(1H, s), 7.5 (1H,                                                         d), 7.25˜6.9                                                            (4H, m), 6.75(1H, b),                                                         6.6(1H, b), 2.8(2H,                                                           t), 2.6 (2H, t),                                                              2.2(3H, s) 1.35(9H,                                                           s)                        2(44)                                                                             ##STR109##          2-methyl-4-[N-(2-chloro-5- carboxyphenyl)sulfamoyl                            ]phenyl ester of pivalic acid                                                                     Rf 0.34 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          8.2(1H,                                                                       b), 7.8˜7.45(3H,                                                         b), 7.3(1H, d),                                                              7.0(1H, d), 2.2(3H,                                                           s), 1.35(9H, s)           2(45)                                                                             ##STR110##          4-[N-(m-carboxyethylphenyl)sulfamoyl] phenyl                                  ester of pivalic acid                                                                             Rf 0.27 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          7.65(2H, d), 7.1(2H,                                                          d), 7.35˜6.8(2H,                                                         m), 6.8˜6.6(2H,                                                         d), 2.85(2H, t),                                                             2.55 (2H, t),                                                                 1.35(9H, s)               2(46)                                                                             ##STR111##          2-methyl-4-[N-(m-sulfonyl)sulfamoyl] phenyl ester                             of pivalic acid     Rf 0.35 (chloroform: methanol:                                                 acetic acid                                                                          (CD.sub.3 SOCD.sub.3)                                                         δ 7.7˜7.6(                                                        2H,                                                                           m), 7.4˜6.9(5H,                                                         m), 2.15(3H, s),                                                              1.30(9H, s)               2(47)                                                                             ##STR112##          2-methyl-4-[N-(2-sulfo-4-methyl- phenyl)sulfamoyl]                            phenyl ester of pivalic acid                                                                      Rf 0.44 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.9˜7.5(3H, m),                                                         .5˜6.9(3H, m),                                                          2.3(3H, s), 2.2(3H,                                                           s), 1.35(9H, s)           2(48)                                                                             ##STR113##          2-methyl-4-[N-(m- carboxymethoxyphenyl)sulfamoyl]                             henyl ester of pivalic acid                                                                       Rf 0.39 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          7.55(1H, s), 7.5(1H,                                                          d), 7.32˜6.5(5H,                                                         m), 6.2(1H, bs),                                                             4.45(2H, s), 2.2 (3H,                                                         s), 1.37(9H, s)           2(49)                                                                             ##STR114##          2-methyl-4-[N-(1,4-dioxa-2-carboxy-8- yl-naphthale                            ne)sulfamoyl]phenyl ester of pivalic                                                              Rf 0.27 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          .6(1H, s), 7.5 (1H,                                                           d), 7.35(1H, d,),                                                             7.2(1H, d, d),                                                                6.9(1H, d), 6.85 (1H,                                                         d), 4.7(1H, s),                                                               4.5(1H, d), 4.1(1H,                                                           d, d), 2.1(1H, s),                                                            1.38(1H, s)               2(50)                                                                             ##STR115##          N-[m-(3-methyl-4-pivaloyloxy- benzene)sulfonylamin                            obenzoyl] glycine   Rf 0.26 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.6˜6.8(7H, m),                                                         .1(2H, s), 2.15(3H,                                                           s), 1.35(9H, s)           2(51)                                                                             ##STR116##          2-methyl-4-[N-(o-carboxypropoxy- phenyl)sulfamoyl]                            phenyl ester of pivalic acid                                                                      Rf 0.45 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.6˜7.3(3H, m),                                                         .1˜6.5(4H, m),                                                          3.8(2H, t), 2.4 (2H,                                                          t), 2.15(3H, s),                                                              2.02(2H, q), 1.35(9H,                                                         s)                        2(52)                                                                             ##STR117##          2-methyl-4-[N-(3,5-dicarboxyphenyl) sulfamoyl]phen                            yl ester of pivalic acid                                                                          Rf 0.39 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          8.38(1H, t), 7.98(2H,                                                         s), 7.8˜7.6(2H,                                                         m), 7.06(1H, d),                                                              2.2(3H, s), 1.38(9H,                                                          s)                        2(53)                                                                             ##STR118##          N-[o-(3-methyl-4-pivaloyloxy-benzene) sulfonylamin                            obenzoyl]glycine    Rf 0.41 (chloroform: methanol:                                                 acetic acid                                                                          ν 2970, 1740,                                                              1630, 1600, 1520,                                                             1480, 1390, 1330,                                                             1260, 1230, 1150,                                                             1090, 930, 760, 590       2(54)                                                                             ##STR119##          2-methyl-4-[N-(1.4-dioxa-2- tetrazolyl-8-yl-naphth                            alene) sulfamoyl]phenyl ester of                                                                  Rf 0.46  (chloroform:                                                         methanol: acetic acid =                                                       30:3:1) (CDCl.sub.3) δ                                                          7.6(1H, s), 7.5(1H,                                                           d), 7.3˜6.7(4H,                                                         m), 5.2(1H, fou),                                                             4.5(2H, eig), 2.1(3H,                                                         s), 1.4(9H, s)            2(55)                                                                             ##STR120##          N-[o-(3-methyl-4-pivaloyloxy- benzene)sulfonylamin                            obenzoyl]-L- valine Rf 0.44 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          7.80(1H,                                                                      d), 7.32˜7.2(4H,                                                         m), 7.15(1H, t), 7.0                                                         1H, d), 6.4(1H, d),                                                           4.5(1H, q), 2.3 (1H,                                                          m), 2.1(3H, s),                                                               1.35(9H, s)               2(56)                                                                             ##STR121##          N-[5-chloro-2-(3-methyl-4- pivaloyloxybenzene)sulf                            onylamino- benzoyl]glycine                                                                        Rf 0.29 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.8˜6.9(7H, m),                                                         .95(2H, s),  2.15(3H,                                                         s), 1.35(9H, s)           2(57)                                                                             ##STR122##          N-[o-(3-methyl-4-pivaloyloxy- benzene)sulfonylamin                            obenzoyl]-dl- alanine                                                                             Rf 0.24 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          7.75(1H, d), 7.6 (1H,                                                         s), 7.65˜7.4                                                            (2H, m),                                                                      7.3˜7.05 (2H,                                                           m), 7.0(1H, d),                                                               6.55(1H, d), 4.6(1H,                                                          q), 2.1 (3H, s),                                                              2.5(3H, d),  1.35(9H,                                                         s)                        2(58)                                                                             ##STR123##          N-[o-(3-methyl-4-pivaloyloxy-benzene) sulfonylamin                            obenzoyl]-β-alanine                                                                          Rf 0.36 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          7.75(1H, d), 7.6 (1H,                                                         s), 7.55˜7.2                                                            (3H, m), 7.1(1H, t),                                                          6.95(1H, d), 6.6 (1H,                                                         b), 3.5(2H, q),                                                               2.6(2H, q), 2.1(3H,                                                           s), 1.35(9H, s)           2(59)                                                                             ##STR124##          2-methyl-4-[N-(2-benzyloxycarbonyl-5- nitrophenyl)                            sulfamoyl]phenyl ester of pivalic                                                                 Rf 0.27 (ethyl acetate:                                                       hexane = 1:5)                                                                         (CDCl.sub.3) δ                                                          8.5(1H, d), 8.1(1H,                                                           d), 7.75(3H, m),                                                              7.4(5H, s), 7.1(1H,                                                           d), 5.4(2H, s)            2(60)                                                                             ##STR125##          N-[2-((3-methyl-4-pivaloyloxybenzene) sulfonylamin                            o)-5-penthyloxybenzoyl] glycine                                                                   Rf 0.22 (ethyl acetate:                                                       hexane: acetic acid =                                                         10:10:0.5)                                                                            (CD.sub.3 OD) δ                                                         .3˜7.6(3H, m),                                                          6.9˜7.2(3H, m),                                                         .95(2H, t), 3.9(2H,                                                           s), 2.15(3H, s)           2(61)                                                                             ##STR126##          N-[5-decyloxy-2-(3-methyl-4- pivaloyloxybenzene)su                            lfonylamino- benzoyl]glycine                                                                      Rf 0.25 (ethyl acetate:                                                       hexane: acetic acid =                                                         10:10:0.5)                                                                            (CD.sub.3 OD) δ                                                         .35˜7.6(3H, m),                                                         .9˜7.2(2H, m),                                                          3.95(2H, t), 3.9(2H,                                                          s), 2.1(3H, s)            2(62)                                                                             ##STR127##          2-methyl-4-[N-(2- prolylcarbonylphenyl)sulfamoyl]                             henyl ester of pivalic acid                                                                       Rf 0.18 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          8.65(1H, s),                                                                  7.8˜ 7.6(3H,                                                            m), 7.4˜                                                                7.0(5H, m), 4.6(1H,                                                           m), 3.25(2H, t),                                                              2.3˜2.1(2H, m),                                                         .15(3H, s),                                                                   2.0˜ 1.7(2H,                                                            m), 1.35 (9H, s)          2(63)                                                                             ##STR128##          N-[o-(p-pivaloyloxybenzene) sulfonylaminobenzoyl]g                            lycine              Rf 0.14 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.8˜7.0(8H, m),                                                         .95(2H, s), 1.30(9H,                                                          s)                        2(64)                                                                             ##STR129##          N-[2-(3-methyl-4-pivaloyloxybenzene) sulfonylamino                            -5-methylbenzoyl]glycine                                                                          Rf 0.20 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          7.7˜6.8(6H, m),                                                         .3(1H, b), 4.0(2H,                                                            d), 2.3(3H, s),                                                               2.1(3H, s), 1.3(9H,                                                           s)                        2(65)                                                                             ##STR130##          N-[o-(3-methyl-4-pivaloyloxybenzene) sulfonylamino                            benzoyl]-1-alanine  Rf 0.24 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          7.8˜6.9(7H, m),                                                         .5(1H, b), 4.6(1H,                                                            b), 2.1(3H, s),                                                               1.45(3H, d), 1.35(9H,                                                         s)                        2(66)                                                                             ##STR131##          N-[5-chloro-2-(3-methyl-4- pivaloyloxybenzene)sulf                            onylamino benzoyl]-1-alanine                                                                      Rf 0.3 (chloroform: methanol:                                                 cetic acid = 100:5:1)                                                                 (CDCl.sub.3) δ                                                          7.75(1H, d), 7.55                                                             (1H, s),                                                                      7.5˜7.3 (3H,                                                            m), 6.95(1H, d),                                                              6.4(1H, b),  4.55(1H,                                                         m), 2.15 (3H, s),                                                             1.45(3H, d), 1.35(9H,                                                         s)                        2(67)                                                                             ##STR132##          N-[o-(3-methyl-4-pivaloyloxybenzene) sulfonylamino                            benzoyl]-L-phenylalanine                                                                          Rf 0.30 (ethyl acetate:                                                       hexane: acetic acid =                                                         10:10:0.5)                                                                            (CD.sub.3 OD) δ                                                         .95˜7.7(12H,                                                            m), 4.6˜4.8(1H,                                                         m), 3.0˜3.4(2H,                                                         m), 2.1(3H, s),                                                               1.35(9H, s)               2(68)                                                                             ##STR133##          N-[o-(3-methyl-4-pivaloyloxybenzene) sulfonylamino                            benzoyl]-dl-methionine                                                                            Rf 0.29 (ethyl acetate:                                                       hexane: acetic acid =                                                         10:10:0.5)                                                                            (CD.sub.3 OD) δ                                                         .55˜7.8(4H, m),                                                         .45(1H, t),                                                                   7.0˜ 7.2(2H,                                                            m), 4.6˜                                                                4.7(1H, m),                                                                   2.4˜ 2.6(2H,                                                            m), 2.13 (3H, s),                                                             2.10(3H, s),                                                                  2.0˜2.3(2H,                                                             m), 1.35(9H, s)           2(69)                                                                             ##STR134##          N-[o-(3-methyl-4-pivaloyloxybenzene) sulfonylamino                            benzoyl]-L-lysine. hydrochloride                                                                  Rf 0.73 (ethyl acetate:                                                       acetic acid: water                                                                    (CD.sub.3 OD) δ                                                         .57˜7.80(3H,                                                            m), 7.35˜7.55(2H                                                        , m), 7.0˜7.22(2                                                        H, m), 4.45˜4.65                                                        (1H, m), 2.95(2H, t),                                                         2.15(3H, s),                                                                  1.4˜2.1(6H, m),                                                         .35 (9H, s)               2(70)                                                                             ##STR135##          2-methyl-4-[N-(2-(N-carboxyphenyl-3- yl)carbamoylp                            henyl)sulfamoyl] phenyl ester of pivalic                                                          Rf 0.52 (ethyl acetate:                                                       hexane: acetic acid =                                                         10:10:0.5)                                                                            ν 1750, 1690,                                                              1540, 1480, 1330,                                                             1300, 1230, 1150,                                                             1110                      2(71)                                                                             ##STR136##          2-methyl-4-[N-(2-carboxymethoxy- phenyl)sulfamoyl]                            phenyl ester of pivalic acid                                                                      Rf 0.21 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          7.7˜6.6(8H,                                                             m),  4.5(2H, s),                                                              2.15(3H, s), 1.3(9H,                                                          s)                        2(72)                                                                             ##STR137##          N-[5-chloro-2-(3-methyl-4- pivaloyloxybenzene)sulf                            onylamino benzoyl]-β-alanine                                                                 Rf 0.28 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          7.8˜7.2(5H, m),                                                         .0(1H, d), 7.6(1H,                                                            b), 3.6(2H, q),                                                               2.64(2H, t), 2.2(3H,                                                          s), 1.35(9H, s)           2(73)                                                                             ##STR138##          2-methyl-4-[N-((2- carboxypropylcarbamoyl-4-chloro                            ) phenyl)sulfamoyl]phenyl ester of pivalic                                                        Rf 0.28 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          7.8˜7.2(5H, m),                                                         .0(1H, d), 6.4 (1H,                                                           b), 3.3(2H, q),                                                               2.5(2H, t), 2.15(3H,                                                          s), 1.9(2H, m),                                                               1.35(9H, s)               2(74)                                                                             ##STR139##          2-methyl-4-[N-(2-(N-carboxyphenyl-4- yl)carbamoylp                            henyl)sulfamoyl] phenyl ester of pivalic                                                          Rf 0.54 (ethyl acetate:                                                       hexane: acetic acid =                                                         10:10:0.5)                                                                            ν 1750, 1680, 1650                                                         590, 1520, 1480,                                                              1400, 1320, 1280,                                                             1250, 1220                2(75)                                                                             ##STR140##          N-[2-(p-pivaloyloxybenzene) sulfonylamino-5-chloro                            benzoyl]glycine     Rf 0.23 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          7.7(2H,                                                                       d), 7.8˜7.6(1H,                                                         m), 7.6˜7.4(2H,                                                         m), 7.08(2H, d),                                                              6.3(1H, b), 4.08(2H,                                                          d), 1.35(9H, s)           2(76)                                                                             ##STR141##          N-[o-(3-methyl-4-pivaloyloxybenzene) sulfonylamino                            benzoyl]tyrosine    Rf 0.27 (ethyl acetate:                                                       hexane: acetic                                                                acid 10:10:0.5)                                                                       (CD.sub.3 OD) δ                                                         .32˜7.7(5H, m),                                                         .0˜7.2(2H, m),                                                          7.05(2H, d), 6.7                                                              (2H, d),                                                                      2.6˜2.75 (1H,                                                           m), 2.87˜4.25                                                           (2H, m), 2.12(3H,                                                             s), 1.35(9H, s)           2(77)                                                                             ##STR142##          N-[o-(3-methyl-4-pivaloyloxybenzene) sulfonylamino                            phenylacetyl]glycine                                                                              Rf 0.44 (ethyl acetate:                                                       acetic acid                                                                           (CD.sub.3 OD) δ                                                         .5˜7.7(2H, m),                                                          7.0˜7.35(5H,                                                            m), 3.9(2H, s),                                                               3.37(2H, s), 2.2(3H,                                                          s), 1.41(9H, s)           2(78)                                                                             ##STR143##          N-[o-(4-pivaloyloxybenzene) sulfonylaminophenylace                            tyl]glycine         Rf 0.37 (ethyl acetate:                                                       acetic acid                                                                           ν 1750, 1610,                                                              1530, 1480, 1400          2(79)                                                                             ##STR144##          4-[N-((2-carboxypropylcarbamoyl-4- chloro)phenyl)s                            ulfamoyl]phenyl ester of pivalic                                                                  Rf 0.47 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.7(2H, d), 7.5 (1H,                                                          s), 7.4˜7.2                                                             (2H, m), 7.1(2H, d),                                                          3.2(2H, t), 2.3(2H,                                                           t), 1.8(2H, m),                                                               1.3(9H, s)                2(80)                                                                             ##STR145##          N-[5-methylthio-2-(p-pivaloyloxy- benzene)sulfonyl                            aminobenzoyl] glycine                                                                             Rf 0.34 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.7(2H, d), 7.6(1H,                                                           d), 7.4˜7.2(2H,                                                         m), 7.1(2H, d),                                                               3.98(2H, s), 2.5(3H,                                                          s), 1.4(9H, s)            2(81)                                                                             ##STR146##          N-[2-(3-methyl-4-pivaloyloxybenzene) sulfonylamino                            -4- trifluoromethylbenzoyl]glycine                                                                Rf 0.12 (ethyl acetate:                                                       hexane: acetic acid =                                                         10:10:0.5)                                                                            (CD.sub.3 OD) δ                                                         .92(1H, s), 7.80 (1H,                                                         d), 7.55˜7.7                                                            (2H, m), 7.45 (1H,                                                            d), 7.11(1H, d),                                                              4.0(2H, s), 2.16(3H,                                                          s) 1.36(9H, s)            2(82)                                                                             ##STR147##          N-[2-(p-pivaloyloxybenzene) sulfonylamino-4-                                  trifluoromethylbenzoyl]glycine                                                                    Rf 0.12 (ethyl acetate:                                                       hexane: acetic acid =                                                         10:10:0.5)                                                                            (CD.sub.3 OD) δ                                                         .95(1H, s), 7.77(2H,                                                          d), 7.80(1H, d),                                                              7.45(1H, d), 7.20(2H,                                                         d), 4.0(2H, s),                                                               1.33(9H, s)               2(83)                                                                             ##STR148##          N-[o-(p-pivaloyloxybenzene) sulfonylaminobenzoyl]-                            S-methyl-L- cysteine                                                                              Rf 0.27 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.8(2H,                                                                       d), 7.7˜7.2(3H,                                                         m), 7.1(2H, d),                                                               7.11(1H, d), 4.8(1H,                                                          m), 3.05(2H, m), 2.15                                                         3H, s), 1.3(9H, s)        2(84)                                                                             ##STR149##          N-[2-(4-pivaloyloxybenzene) sulfonylaminobenzoyl]                             -L-methionine       Rf 0.34 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.8(2H,                                                                       d), 7.7˜7.2(3H,                                                         m), 7.1(2H, d),                                                               7.11(1H, d), 4.7(1H,                                                          m), 2.8˜2.0                                                             (4H, m), 2.14(3H, s),                                                         .3(9H, s)                 2(85)                                                                             ##STR150##          N-[5-decyloxy-2-(p- pivaloyloxybenzene) sulfonylam                            inobenzoyl]glycine  Rf 0.49 (ethyl acetate:                                                       hexane: acetic acid =                                                         10:10:0.5)                                                                            ν 3449, 2926,                                                              1762, 1728, 1645,                                                             1607, 1530, 1501,                                                             1252                      2(86)                                                                             ##STR151##          N-[2-(3-methyl-4-pivaloyloxybenzene) sulfonylamino                            -5-methylthiobenzoyl] glycine                                                                     Rf 0.25 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.7˜7.2(5H, m),                                                         .95(1H, d), 2.95(2H,                                                          s), 2.5(3H, s),                                                               2.2(3H, s),  1.35(9H,                                                         s)                        2(87)                                                                             ##STR152##          N-[2-(p-pivaloyloxybenzene) sulfonylamino-5-propyl                            thiobenzoyl] glycine                                                                              Rf 0.29 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.75(2H,                                                                      d), 7.6˜7.1(3H,                                                         m), 7.1(2H, d),                                                               4.0(2H, s), 2.9(2H,                                                           t), 1.8˜1.5(2H,                                                         m), 1.35(9H, s),                                                              1.0(3H, t)                2(88)                                                                             ##STR153##          N-[o-(p-pivaloyloxybenzene) sulfonylaminobenzoyl]-                            2R- phenylglycine   Rf 0.19 (ethyl acetate:                                                       hexane: acetic acid =                                                         10:10:0.5)                                                                            (CD.sub.3 OD) δ                                                         .55˜7.7(4H, m),                                                         .2˜7.7(6H, m),                                                          7.15(1H, t), 6.97(2H,                                                         d), 5.57(1H, s),                                                              1.3(9H, s)                2(89)                                                                             ##STR154##          N-[o-(3-methyl-4-pivaloyloxybenzene) sulfonylamino                            benzoyl]-2R- phenylglycine                                                                        Rf 0.2 (ethyl acetate:                                                        hexane: acetic acid =                                                         10:10:0.5)                                                                            (CD.sub.3 OD) δ                                                         .2˜7.8(10H, m),                                                         .12(1H, t), 6.90(1H,                                                          d), 5.57(1H, s),                                                              2.06(3H, s), 1.35(9H,                                                         s)                        2(90)                                                                             ##STR155##          N-[5-methyl-2-(p-pivaloyloxybenzene) sulfonylamino                            -benzoyl]glycine    Rf 0.27 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.7(2H, d), 7.5(1H,                                                           s), 7.3˜7.1(2H,                                                         b), 7.0(2H, d),                                                               3.95(2H, s), 2.3(3H,                                                          s), 1.3(9H, s)            2(91)                                                                             ##STR156##          4-[N-(o-(N-carboxyphenyl-3-yl) carbamoylphenyl)sul                            famoyl]phenyl ester of pivalic acid                                                               Rf 0.32 (chloroform: methanol:                                                 acetic acid                                                                          ν 1752, 1692,                                                              1646, 1595, 1554,                                                             1491, 1409, 1338,                                                             1304, 1259, 1209          2(92)                                                                             ##STR157##          N-[2-(p-pivaloyloxybenzene) sulfonylaminobenzoyl]g                            lycine methyl ester Rf 0.77 (chloroform: methanol:                                                 = 10:1)                                                                              (CDCl.sub.3) δ                                                          7.7(2H, d), 7.65(1H,                                                          b), 7.55˜7.3(2H,                                                         m), 7.2˜7.0(1H,                                                         m), 7.0(2H, d),                                                              4.0(2H, d), 3.8 (3H,                                                          s), 1.35(9H, s)           2(93)                                                                             ##STR158##          2-[N-(2-(4-pivaloyloxybenzene) sulfonylaminobenzoy                            l)glycyloxy]-N,N- dimethylacetamide                                                               Rf 0.53 (chloroform: methanol                                                 = 10:1) (CDCl.sub.3) δ                                                          7.7(2H,                                                                       d), 7.8˜7.6(1H,                                                         b), 7.55˜7.2(2H,                                                         m), 7.2˜7.0(1H,                                                         m), 7.05(2H, d), 4.8                                                         2H, s), 4.2(2H, d),                                                           3.0(6H, s), 1.35(9H,                                                          s)                        2(94)                                                                             ##STR159##          N-[5-pentyloxy-2-(p- pivaloyloxybenzene) sulfonyla                            minobenzoyl]glycine Rf 0.26 (ethyl acetate:                                                       hexane: acetic acid =                                                         10:10:0.5)                                                                            (CDCl.sub.3) δ                                                          7.65(2H, d), 7.50                                                             (1H, d), 7.18(2H, d),                                                         .11(1H, s), 7.02(1H,                                                          dd), 3.95(2H, t),                                                             3.88 (2H, s),                                                                 1.65˜1.85 (2H,                                                          m), 1.25˜1.55                                                           (4H, m), 1.33(9H, s),                                                         .92(3H, t)                2(95)                                                                             ##STR160##          2-methyl-4-[N-((2-benzyloxy-carbonyl- 4-chloro)phe                            nyl)sulfamoyl]phenyl ester of pivalic                                                             Rf 0.30 (ethyl acetate:                                                       hexane: = 1:10)                   2(96)                                                                             ##STR161##          2-methyl-4-[N-((2-benzyloxy-carbonyl- 4-methyl)phe                            nyl)sulfamoyl]phenyl ester of pivalic                                                             Rf 0.28 (ethyl acetate:                                                       hexane: = 1:10)                   2(97)                                                                             ##STR162##          2-isopropyl-4-[N-(o- benzyloxycarbonylphenyl)sulfa                            moyl] phenyl ester of pivalic acid                                                                Rf 0.32 (ethyl acetate:                                                       hexane: = 1:10)                   2(98)                                                                             ##STR163##          2-isopropyl-4-[N-((2- benzyloxycarbonyl-4-chloro)p                            henyl) sulfamoyl]phenyl ester of                                                                  Rf 0.35 (ethyl acetate:                                                       hexane: = 1:10)                   2(99)                                                                             ##STR164##          2-methyl-4-[N-(2-benzyloxycarbonyl- phenyl)sulfamo                            yl]phenyl ester of pivalic acid                                                                   Rf 0.58 (ethyl acetate:                                                       hexane: = 1:10)                   2(100)                                                                            ##STR165##          2-methyl-4-[N-(2,5-dibenzyloxy- carbonylphenyl)sul                            famoyl]phenyl ester of pivalic acid                                                               Rf 0.12 (ethyl acetate:                                                       hexane: 1:10)                     2(101)                                                                            ##STR166##          2-methyl-4-[N-(3- benzyloxycarbonylphenyl)sulfamoy                            l] phenyl ester of pivalic acid                                                                   Rf 0.37 (ethyl acetate:                                                       hexane: = 2:5)                    2(102)                                                                            ##STR167##          2-methyl-4-[N-((2-benzyloxycarbonyl- 4-hydroxy)phe                            nyl)sulfamoyl] phenyl ester of pivalic                                                            Rf 0.18 (methylene chloride:                                                  methanol = 10:1)                  2(103)                                                                            ##STR168##          2,6-dimethyl-4-[N-(o- benzyloxycarbonylphenyl)sulf                            amoyl] phenyl ester of pivalic acid                   2(104)                                                                            ##STR169##          2-methyl-4-[N-((4-acetyloxy-2- benzyloxycarbonyl)p                            henyl)sulfamoyl] phenyl ester of pivalic                                                          Rf 0.39 (chloroform: methanol                                                 =  10:1)                          2(105)                                                                            ##STR170##          2-methyl-4-[N-((2-benzyloxycarbonyl- 4-hexanoyloxy                            )phenyl)sulfamoyl] phenyl ester of pivalic                                                        Rf 0.44 (mchloroform:                                                         methanol = 10:1)                  2(106)                                                                            ##STR171##          2-methyl-4-[N-(2,6-dibenzyloxy- carbonylphenyl)sul                            famoyl]phenyl ester of pivalic acid                                                               Rf 0.12 (hexane: ethyl                                                        acetate = 10:1)                   2(107)                                                                            ##STR172##          o-(3-methyl-4-pivaloyloxybenzene) sulfonylaminoben                            zoyloxy acetic acid benzylester                                                                   Rf 0.41 (hexane: ethyl                                                        acetate = 5:2)                    2(114)                                                                            ##STR173##           N-[o-(p-pivaloyloxybenzene) sulfonylaminobenzoyl]                            -2S-phenyl glycine  Rf 0.31 (ethyl acetate:                                                       hexane: acetic acid =                                                         10:10:0.5)                                                                            ν 1751, 1641,                                                              1594, 1520, 1493,                                                             1456, 1398, 1340,                                                             1275, 1207, 1164,                                                             1104                      2(115)                                                                            ##STR174##          N-[o-(p-pivaloyloxybenzene) sulfonylaminobenzoyl]-                            L-leucine           Rf 0.45 (Chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          7.75(2H,                                                                      d), 7.85˜7.60(1H                                                        , m), 7.6˜7.15(3                                                        H, m), 7.05(2H, d),                                                           6.40 (1H, b), 5.4(1H,                                                         b), 4.6(1H, m),                                                               2.0˜1.4 (3H,                                                            b), 1.35(9H, s),                                                              1.0(6H, d)                2(116)                                                                            ##STR175##          N-[o-(p-pivaloyloxybenzene) sulfonylaminobenzoyl]g                            lycinamide          Rf 0.28 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD +                                                                 CD.sub.3 SOCD.sub.3)                                                          δ 7.75(2H, d),                                                          7.65˜7.35(3H,                                                           m), 7.1(2H, d),                                                               7.2˜7.0(1H, b),                                                         .95(2H, s), 1.35(9H,                                                          s)                        2(117)                                                                            ##STR176##          N-[o-(p-pivaloyloxybenzene) sulfonylaminobenzoyl]-                            L-alanine           Rf 0.28 (chloroform: methanol                                                 cetic acid = 100:5:1)                                                                 (CDCl.sub.3) δ                                                          7.75(2H,                                                                      d), 7.8˜7.7(1H,                                                         b), 7.5˜7.4(2H,                                                         m), 7.05(2H, d),                                                              7.2˜ 7.1(1H,                                                            m), 6.5(1H, d),                                                               4.6(1H, q), 1.5 (3H,                                                          d), 1.35(9H, s)           2(118)                                                                            ##STR177##          N-[o-(p-pivaloyloxybenzene) sulfonylaminobenzoyl]-                            β-alanine      Rf 0.48 (Chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          7.7(2H,                                                                       d), 7.8˜7.7(1H,                                                         b), 7.45(1H, t), 7.3                                                          (1H, d), 7.2(1H, t),                                                          7.1(1H, d), 7.05 (2H,                                                         d), 6.6(1H, b),                                                               3.5(2H, q), 2.6 (2H,                                                          t), 1.35(9H, s)           2(119)                                                                            ##STR178##          p-[N-(o-carboxyethoxyphenyl) sulfamoyl]phenyl                                 ester of pivalic acid                                                                             Rf 0.36 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          7.7(2H,                                                                       d), 7.75˜7.65(1H                                                        , b), 7.2˜7.0(5H                                                        , m), 6.8(1H, d),                                                             4.0(2H, t), 2.6(2H,                                                           t), 1.35(9H, s)           2(120)                                                                            ##STR179##          N-[o-(p-pivaloyloxybenzene) sulfonylaminobenzoyl]-                            S-valine            Rf 0.34 (acetic acid:                                                         chloroform = 1:19)                                                                    ν 2972, 1752,                                                              1640, 1595, 1527,                                                             1492, 1398                2(121)                                                                            ##STR180##          p-[N-(o-carboxypropoxyphenyl) sulfamoyl]phenyl                                ester of pivalic acid                                                                             Rf 0.48 (Chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          7.7(2H, d), 7.45(1H,                                                          d, d), 7.0(2H, d),                                                            7.1˜6.5(5H, m),                                                         .8(2H, t), 2.4(2H,                                                            t), 2.0(2H, b),                                                               1.35(9H, s)               2(122)                                                                            ##STR181##          N-methyl-N-[o-(p-pivaloyloxybenzene) sulfonylamino                            benzoyl]glycine     Rf 0.17 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD + D.sub.2                                                         O) δ 7.8(2H,                                                            d), 7.8˜7.5(1H,                                                         b), 7.1(2H, d),                                                               7.4˜7.0(4H, m),                                                         .1(2H, s), 2.7(3H,                                                            s), 1.35(9H, s)           2(123)                                                                            ##STR182##          N-[o-(p-pivaloyloxybenzene) sulfonylaminobenzoyl]-                            L-phenylalanine     Rf 0.36 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.7(2H, d), 7.6(1H,                                                           d), 7.05(2H, d),                                                              7.4˜6.8(8H, m),                                                         .8(1H, b), 3.2(2H,                                                            m), 1.35(9H, s)           2(124)                                                                            ##STR183##          N-[o-(p-pivaloyloxybenzene) sulfonylaminobenzoyl]-                            D-phenylalanine     Rf 0.36 (Chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.7(2H, d), 7.6(1H,                                                           d), 7.05(2H, d),                                                              7.4˜6.8(8H, m),                                                         .8(1H, b), 3.2(2H,                                                            m), 1.35(9H, s)           2(125)                                                                            ##STR184##          N-[o-(p-pivaloyloxybenzene) sulfonylaminobenzoyl]-                            L-tryptophan        Rf 0.25 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.75(2H, d), 7.6(1H,                                                          d), 7.0(2H, d),                                                               7.6˜6.8(8H, m),                                                         .85(1H, b), 3.35(2H,                                                          d), 1.35(9H, s)           2(126)                                                                            ##STR185##          N-[o-(N-methyl-N-(p- pivaloyloxybenzene) sulfonyla                            minobenzoyl)]glycine                                                                              Rf 0.46 (chloroform: methanol:                                                 THF = 30:3:1)                                                                        ν 3391, 2977,                                                              1756, 1662, 1597,                                                             1535, 1482, 1405          2(127)                                                                            ##STR186##          dl-3-phenyl-3-[o-(p- pivaloyloxybenzene) sulfonyla                            minobenzoyl]amino propionic acid                                                                  Rf 0.5 (Chloroform: methanol:                                                 cetic acid = 100:5:1)                                                                 (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.6(2H,                                                                       d), 7.7˜7.5(1H,                                                         m), 7.5˜7.1(7H,                                                         m), 7.0(1H, d, d),                                                            6.9(2H, d),  5.5(1H,                                                          b), 2.9(2H, d),                                                               1.35(9H, s)               2(128)                                                                            ##STR187##          N-[o-(p-pivaloyloxybenzene) sulfonylaminobenzoyl]-                            4-piperidine carboxylic acid                                                                      Rf 0.5 (chloroform: methanol:                                                 cetic acid = 100:5:1)                                                                 (CDCl.sub.3 +                                                                 CD.sub.3 OD)  δ                                                         .7(1H,                                                                        d), 7.6˜7.4(1H,                                                         m), 7.4˜7.2(1H,                                                         m), 7.2˜6.9(4H,                                                         m), 4.0˜3.6(1H,                                                         b), 2.9˜2.4(4H,                                                         b), 2.0˜1.4(4H,                                                         b), 1.35(9H, s)           2(129)                                                                            ##STR188##          N-[o-(p-pivaloyloxybenzene) sulfonylaminobenzoyl]-                            D-methionine        Rf 0.45 (chloroform: methanol                                                 cetic acid = 100:5:1)                                                                 (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.8(2H,                                                                       d), 7.7˜7.1(4H,                                                         m), 7.1(2H, d),                                                               4.7(1H, b), 2.9(3H,                                                           s), 2.6˜1.9(4H,                                                         m), 1.35(9H, s)           2(130)                                                                            ##STR189##          N-[o-(p-pivaloyloxybenzene) sulfonylaminobenzoyl]-                            D-valine            Rf 0.46 (ethyl acetate:                                                       n-hexane: acetic acid =                                                       10:10:0.5)                                                                            ν 3392, 2973,                                                              1746, 1641, 1595,                                                             1528, 1493, 1398          2(131)                                                                            ##STR190##          p-[N-(o-carboxypropylcarbamoylphenyl) sulfamoyl]ph                            enyl ester of pivalic acid                                                                        Rf 0.36 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.7(2H,                                                                       d), 7.7˜7.5(1H,                                                         b), 7.4˜7.2(2H,                                                         m), 7.0(2H, d), 7.1                                                           (1H, d), 3.3(2H, t),                                                          2.4(2H, t), 1.9 (2H,                                                          q), 1.35(9H, s)           2(132)                                                                            ##STR191##          p-[N-(o-carboxyheptylcarbamoylphenyl) sulfamoyl]ph                            enyl ester of pivalic acid                                                                        Rf 0.38 (chloroform: methanol                                                 cetic acid = 100:5:1)                                                                 (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.7(2H,                                                                       d), 7.7˜7.6(1H,                                                         b), 7.4˜7.2(2H,                                                         m), 7.0(2H, d), 7.1                                                           (1H, b), 3.2(2H, b),                                                          2.3(2H, b),                                                                   1.9˜1.2 (6H,                                                            b), 1.35(9H, s)           2(133)                                                                            ##STR192##          N-[ o-(p-pivaloyloxybenzene) sulfonylaminobenzoyl]                            -D-alanine          Rf 0.28 (chloroform: methanol                                                 cetic acid = 100:5:1)                                                                 (CDCl.sub.3 +                                                                 CD.sub.3 OD)) δ                                                         .75(2H,                                                                       d) 7.8˜7.7(1H,                                                          b), 7.5˜7.4(2H,                                                         m), 7.05(2H, d),                                                              7.2˜7.1(1H, m),                                                         .6(1H, m), 1.5(3H,                                                            d), 1.35(9H, s)           2(134)                                                                            ##STR193##          N-[(p-pivaloyloxybenzene)sulfonyl]-4- piperidine                              carboxylic acid     Rf 0.4 (chloroform: methanol:                                                 cetic acid = 100:5:1)                                                                 (CDCl.sub.3) δ                                                          7.75(2H, d), 7.2(2H,                                                          d), 3.6(2H, b),                                                               2.7˜2.0(3H, m),                                                         .0˜1.6(4H, m),                                                          1.20(9H, s)               2(135)                                                                            ##STR194##          4-[(p-pivaloyloxybenzene) sulfonylamino]-2-naphtoi                            c acid              Rf 0.4 (chloroform: methanol                                                  acetic acid                                                                           (CDCl.sub.3) δ                                                          8.9(1H, d), 8.1(1H,                                                           d), 7.75(2H, d),                                                              8.0˜7.8(1H, b),                                                         .6˜7.3(3H, m),                                                          7.0(2H, d),  1.35(9H,                                                         s)                        __________________________________________________________________________     *The number of the carbon atoms of benzene ring were named from a carbon      atom conbined with the oxygen atom in pivaloyl group as first.           

                                      TABLE V                                     __________________________________________________________________________     ##STR195##                                                                    Example                                                                            ##STR196##                              IR (cm.sup.-1)                  No.  R.sup.3 *      Name             TLC     or NMR                           __________________________________________________________________________    2(108)                                                                              ##STR197##    2-chloro-4-[N-(p-tolyl)carbamoyl] phenyl ester of                             pivalic acid     Rf 0.77 (methylene chloride: acetic                                           acid = 30:1)                                                                          (CDCl.sub.3) δ 7.5(2H,                                                  b), 7.2˜6.5(5H, m),                                                     6.2(2H, b), 2.1(3H, s),                                                       1.3(9H, s)                       2(109)                                                                              ##STR198##    2-methoxy-p-[N-(p-tolyl)carbamoyl] phenyl ester of                            pivalic acid      Rf 0.74 (methylene chloride: acetic                                          acid = 30:1)                                                                          ν 3200, 2980, 1750, 1640,                                                  1600, 1510, 1400, 1330,                                                       1280, 1110                       2(110)                                                                              ##STR199##    4-[N-(o-benzyloxycarbonylphenyl) carbamoyl]phenyl                             ester of pivalic acid                                                                          Rf 0.83 (methylene chloride: acetic                                           acid = 30:1)                             2(111)                                                                              ##STR200##    4-[N-(2-pyridyl)carbamoyl]phenyl ester of pivalic                             acid             Rf 0.30 (chloroform methanol = 10:1)     2(112)                                                                              ##STR201##    3-acetyloxy-4-[(N-methyl-N-phenyl) carbamoyl]phenyl                           ester of pivalic acid                                                                          Rf 0.24 (methylene chloride: acetic                                           acid = 30:1)                                                                          (CHDl.sub.3) δ                                                          7.1˜7.5(6H, m),                                                         6.7˜7.0(2H, m),                                                         3.5(3H, s), 2.3(3H, s),                                                       1.3(9H, s)                       2(113)                                                                              ##STR202##    4-[N-(m-benzyloxycarbonylphenyl) carbamoyl]phenyl                             ester of pivalic acid                                                                          Rf 0.38 (methylene chloride: acetic                                           acid: = 30:1)                            __________________________________________________________________________

EXAMPLE 3 P-[N-(p-(p-guanidinobenzoyloxy)phenyl)sulfamoyl]phenyl esterof pivalic acid ##STR203##

p-Guanidinobenzoyl chloride hydrochloride (800 mg) was added to pyridinesolution (5 ml) of the compound of the present invention (500 mg)obtained in Example 2(7) under cooling with ice, and the mixture wasstirred for 2 hours.

After reaction, ether was added to the reaction mixture and thesupernatant was decanted. Saturated aqueous solution of sodiumbicarbonate was added to the residue to obtain oily carbonate.

Further, the supernatant was decanted and the residue was purified bycolumn chlomatography on silica-gel (ethyl acetate:aceticacid:water=400:100:30) to give tile title compound (532 mg) having tilefollowing physical data.

TLC: Rf 0.80 (ethyl acetate: acetic acid: water=3:1:1);

IR: ν 3600˜2300, 1750˜1700, 1680, 1500, 1400.

EXAMPLE 4 p-[N-(p-benzyloxycarbonylphenyl)sulfamoyl)phenyl ester ofpivalic acid ##STR204##

The title compound (210 mg, same as compound obtained in Example 1(5))was obtained by the same procedure as Reference Example 1→Example 1, byusing a corresponding sulfonylchloride compound as starting material.

The compounds of the present invention were obtained by the sameprocedure as Example 4, by using a corresponding amine and pivaloylchloride.

                                      TABLE VI                                    __________________________________________________________________________     ##STR205##                                                                    Example                                                                            ##STR206##                                      IR (cm.sup.-1)          No.  R.sup.3 *           Name               TLC      or                       __________________________________________________________________________                                                         NMR                      4(1)                                                                                ##STR207##         p-[N-((1-benzyloxycarbonyl-1-benzyl) methyl)sulfa                             moyl]phenyl ester of pivalic acid                                                                Rf 0.47 (hexane: ethyl                                                        acetate = 5:2)                    4(2)                                                                                ##STR208##         p-[N-((1-benzyloxycarbonyl-1-phenyl) methyl)sulfa                             moyl]phenyl ester of pivalic acid                                                                Rf 0.40 (hexane: ethyl                                                        acetate = 5:2)                    4(3)                                                                                ##STR209##         p-[N-((o-benzyloxycarbonyl)phenyl) sulfamoyl]phen                             yl ester of pivalic acid                                                                         Rf 0.62 (hexane: ethyl                                                        acetate = 5:2)                    4(4)                                                                                ##STR210##         2-nethyl-4-[N-((o-benzyloxycarbonyl) phenyl)sulfa                             moyl]phenyl ester of pivalic acid                                                                Rf 0.62 (hexane: ethyl                                                        acetate = 5:2)                    4(5)                                                                                ##STR211##         p-(N-phenethylsulfamoyl)phenyl ester of pivalic                               acid               Rf 0.41 (hexane: ethyl                                                        acetate = 5:2)                                                                         δ 7.85(2H, d),                                                          .4˜7.0(7H, m),                                                          .5˜4.2(1H, b),                                                          .4˜3.1(2H, m),                                                          .8(2H, t), 1.35(9H,                                                           s)                       4(6)                                                                                ##STR212##         p-(N-benzylsulfamoyl)phenyl ester of pivalic                                  acid               Rf 0.47 (hexane: ethyl                                                        acetate = 5:2)                                                                         δ  7.9(2H, d),                                                          .4˜7.2(7H, m),                                                          .7(1H, b), 4.2(2H,                                                            d), 1.35(9H,             __________________________________________________________________________                                                         s)                   

EXAMPLE 5 p-[N-(p-carboxyphenyl)sulfamoyl]phenyl ester of pivalic acid##STR213##

In an atmosphere of hydrogen gas, the mixture solution of benzylcompound (190 mg) of Example 4, 10% Pd-carbon (30 mg), acetic acid (10ml) and THF (4 ml) was stirred for 3 hours at room temperature.

The reaction solution was filtered off, and tile filtrate was carriedout azeotropic concentration by mixture of toluene-THF, and theazeotropic concentrate was recrystallized by mixture of ethylacetatehexane to give title compound (143 mg) having the followingphysical data.

TLC: Rf 0.56 (ethyl acetate:hexane=1:1);

IR: ν 2700˜2400, 1750, 1680, 1600, 1340, 1290, 1200, 1160, 1110 cm⁻¹.

Hereinafter, by the same procedure of Example 5, using correspondingbenzyl compound, compounds of the present invention described in thefollowing Table VII were obtained.

                                      TABLE VII                                   __________________________________________________________________________     ##STR214##                                                                    No.Example                                                                         ##STR215##         Name                TLC     or NMRIR                 __________________________________________________________________________                                                        (cm.sup.-1)               5(1)                                                                                ##STR216##        p-[N-(α-carboxyphenethyl)sulfamoyl] phenyl                              ester of pivalic acid                                                                             Rf 0.34 (chloroform: methanol:                                                 acetic acid                                                                          δ 7.8(2H, d),                                                           7.4˜7.0(7H, m),                                                         .2(1H, b), 4.2(1H,                                                            b), 3.2˜3.0(2H,                                                         b), 1.4(9H, s)            5(2)                                                                                ##STR217##        p-[N-(α-carboxyben zyl)sulfamoyl] phenyl                                ester of pivalic acid                                                                             Rf 0.44 (chloroform: methanol:                                                 acetic acid                                                                          δ 7.8(2H, d),                                                           7.35(5H, bs),                                                                 7.15(2H, d), 5.75(1H,                                                         d), 5.15(1H, d),                                                              1.35(9H, s)               5(3)                                                                                ##STR218##        p-[N-(o-carboxyphenyl)sulfamoyl] phenyl ester of                              pivalic acid        Rf 0.37 (chloroform: methanol:                                                 acetic acid                                                                          δ 8.2˜7.0(                                                        8H, m), 5.5(1H, b),                                                           1.35(9H, s)               5(4)                                                                                ##STR219##        2-methyl-4-[N-(o-carboxyphenyl) sulfamoyl]phenyl                              ester of pivalic acid                                                                             Rf 0.25 (chloroform: methanol:                                                 acetic acid                                                                          δ 8.05(1H, d),                                                          7.9˜7.3(5H, m),                                                         .3˜7.0(2H, m),                                                          2.2(3H, s), 1.35(9H,                                                          s)                        5(5)                                                                                ##STR220##        2-methyl-4-[N-(2-carboxy-4- chlorophenyl)sulfamoyl                            ]phenyl ester of pivalic acid                                                                     Rf 0.26 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          8.0(1H,                                                                       d), 7.8˜7.6(3H,                                                         m), 7.45(1H, d, d),                                                           7.1(1H, d), 2.2(3H,                                                           s), 1.4(9 H, s)           5(6)                                                                                ##STR221##        2-methyl-4-[N-(2-carboxy-4- methylphenyl)sulfamoyl                            ]phenyl ester of pivalic acid                                                                     Rf 0.41 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          7.9˜7.5(4H, m),                                                         .38(1H, d), 7.1(1H,                                                           d), 2.35(3H, s),                                                              2.2(3H, s), 1.35(9H,                                                          s)                        5(7)                                                                                ##STR222##        2-isopropyl-4-[N-(o-carboxyphenyl) sulfamoyl]pheny                            l ester of pivalic acid                                                                           Rf 0.32 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          8.0(1H,                                                                       d), 7.9˜7.5(4H,                                                         m), 7.25(1H, d),                                                              7.1(1H, d), 3.0(1H,                                                           b), 1.35(9H, s),                                                              1.15(6H, d)               5(8)                                                                                ##STR223##        2-isopropyl-4-[N-(2-carboxy-4- chlorophenyl)sulfam                            oyl]phenyl ester of pivalic acid                                                                  Rf 0.32 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          7.95(1H,                                                                      d), 7.85˜7.4(4H,                                                         m), 7.05(1H, d),                                                             3.0(1H, b), 1.35(9H,                                                          s), 1.15(6H, d)           5(9)                                                                                ##STR224##        2-methyl-4-[N-(2-carboxynaphthyl) sulfamoyl]phenyl                             ester of pivalic acid                                                                            Rf 0.33 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          8.6(1H, s), 8.05(1H,                                                          s), 7.9˜7.3(6H,                                                         m), 7.0(1H, d),                                                               2.1(3H, s), 1.35(9H,                                                          s)                        5(10)                                                                               ##STR225##        2-methyl-4-[N-(2,5-dicarboxyphenyl) sulfamoyl]phen                            yl ester of pivalic acid                                                                          Rf 0.26 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          8.3(1H, d), 8.0(1H,                                                           d), 7.8˜7.6(3H,                                                         m), 7.03(1H, d),                                                              2.2(3H, s), 1.35(9H,                                                          s)                        5(11)                                                                               ##STR226##        2-methyl-4-[N-(3-carboxypyridine-2- yl)sulfamoyl]p                            henyl ester of pivalic acid                                                                       Rf 0.48 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          8.3(2H, m), 8.0(1H,                                                           s), 7.9(1H, d),                                                               6.95(1H, d, d),                                                               2.25(3H, s), 1.35(9H,                                                         s)                        5(12)                                                                               ##STR227##        2-methyl-4-[N-(2-carboxy-4- hydroxyphenyl)sulfamoy                            l]phenyl ester of pivalic acid                                                                    Rf 0.31 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3 +                                                                 CD.sub.3 OD) δ                                                          7.7˜7.4(3H, m),                                                         .32(1H,                                                                       d), 7.1˜6.8(2H,                                                         m), 2.15(3H, s),                                                              1.35(9H, s)               5(13)                                                                               ##STR228##        2,6-dimethyl-4-[N-(o-carboxyphenyl) sulfamoyl]phen                            yl ester of pivalic acid                                                                          Rf 0.28 (ethyl acetate:                                                       hexane: acetic acid =                                                         10:20:0.5)                                                                            ν 3500˜2500,                                                         1750, 1660, 1580,                                                             1480, 1420, 1340,                                                             1250, 1150, 1100          5(14)                                                                               ##STR229##        2-methyl-4-[N-(2-carboxy-4- acetyloxyphenyl)sulfam                            oyl]phenyl ester of pivalic acid                                                                  Rf 0.33 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          7.8˜7.1(5H, m),                                                         .0(1H, d), 2.3(3H,                                                            s), 2.15(3H, s),                                                              1.35(9H, s)               5(15)                                                                               ##STR230##        2-methyl-4-[N-(2-carboy-4- hexanoyloxyphenyl)sulfa                            moyl] phenyl ester of pivalic acid                                                                Rf 0.33 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          7.75˜7.40(4H,                                                           m), 7.15(1H, d, d),                                                           6.95(1H, d), 2.45(2H,                                                         t), 2.1(3H, s),                                                               1.35(9H, s), 0.85(3H,                                                         t)                        5(16)                                                                               ##STR231##        2-methyl-4-[N-(2,5-dicarboxyphenyl) sulfamoyl]phen                            yl ester of pivalic acid                                                                          Rf 0.37 (chloroform: methanol:                                                 acetic acid                                                                          ((CD.sub.3).sub.2 SO)                                                         δ 7.98(2H, d),                                                          7.4˜7.2(3H, m),                                                         .0(1H, d), 2.1(3H,                                                            s), 1.36(9H, s)           5(17)                                                                               ##STR232##        o-(3-methyl-4-pivaloyloxybenzene) sulfonylaminoben                            zoyloxy acetic acid Rf 0.33 (chloroform: methanol:                                                 acetic acid                                                                          (CDCl.sub.3) δ                                                          8.0˜6.85(7H,                                                            m), 4.75(2H, s),                                                              2.15(3H, s), 1.35(9H,                                                         s)                        __________________________________________________________________________

                                      TABLE VIII                                  __________________________________________________________________________     ##STR233##                                                                    Example                                                                            ##STR234##                           IR (cm.sup.-1)                     No.  R.sup.3 *   Name             TLC     or NMR                              __________________________________________________________________________    5(18)                                                                               ##STR235## p-[N-(o-carboxyphenyl)carbamoyl] phenyl ester of pivalic                      acid             Rf 0.42 (ethyl acetate: hexane: acetic                                        acid = 10:20:0.5)                                                                     ν 1740, 1680, 1660, 1600,                                                  1590, 1540, 1480, 1440              5(19)                                                                               ##STR236## p-[N-(methyl-N-(o-carboxyphenyl) carbamoyl]phenyl ester                       of pivalic acid  Rf 0.17 (ethyl acetate: hexane: acetic                                        acid = 10:20:0.5)                                                                     ν 1750, 1720, 1590, 1470,                                                  1440, 1380                          5(20)                                                                               ##STR237## p-[N-(methyl-N-(m-carboxyphenyl) carbamoyl]phenyl ester                       of pivalic acid  Rf 0.15 methylene chloride: ethyl                                             acetate = 30:1)                                                                       ν 1750, 1720, 1640, 1600,                                                  1580, 1480, 1440,                   __________________________________________________________________________                                              1370                            

EXAMPLE 6 p-[(N-methyl-N-phenyl)sulfamoyl]phenyl ester of pivalic acid##STR238##

In an atmosphere of argon, THF solution (8 ml) of the compound of thepresent invention of Example 1 (1) (300 mg) was added to sodium hydride(37 mg) under cooling with ice, and the mixture was stirred for hours.

Methyl iodide (66 μl) and hexamethylphosphoramide (HMPA) (1 ml) wereadded to the reaction solution, and the mixture was stirred for 30minutes.

The reaction solution was extracted with ether, and the extract waswashed with successive, water and saturated aqueous solution of sodiumchloride.

And further, the solution was dried with sodium sulfate, and distilledoff under reduced pressure to give the title compound (180 mg) havingthe following physical data.

TLC: Rf 0.61 (methylene chloride: ethyl acetate: 30:1);

IR: ν 1750, 1590, 1490, 1450, 1340 cm⁻¹.

Hereinafter, by tile same procedure of Example 6, using correspondingderivative of pivalic acid, the compounds of the present inventiondescribed in Table VIII were obtained.

                                      TABLE VIII                                  __________________________________________________________________________     ##STR239##                                                                    Example                                                                            ##STR240##                                      IR (cm.sup.-1)          No.  R.sup.3 *           Name                TLC     or                       __________________________________________________________________________                                                         NMR                      6(1)                                                                                ##STR241##         p-[N-methyl-N-(p-tolyl)carbamoyl] phenyl ester                                of pivalic acid     Rf 0.33 (methylene chloride:                                                  cetic acid                                                                            ν 1750, 1640,                                                              1600, 1510, 1360,                                                             1200 (neat)              6(2)                                                                                ##STR242##         p-[N-methyl-N-(o-benzyloxy- carbonylphenyl)carbam                             oyl]phenyl ester  of pivalic acid                                                                 Rf 0.21 (methylene chloride:                                                  cetic acid                                                                            ν 1750, 1720,                                                              1640, 1600, 1370,                                                             1250 (neat)              6(3)                                                                                ##STR243##         p-[N-methyl-N-(m- benzyloxycarbonylphenyl)carbamo                             yl] phenyl ester of pivalic acid                                                                  Rf 0.38 (methylene chloride:                                                  cetic acid = 30:1)               6(4)                                                                                ##STR244##         p-[N-methyl-N-(pyridine-3-yl) carbamoyl]phenyl                                ester of pivalic acid                                                                             Rf 0.44 (chloroform:                                                          methanol = 10:1)                                                                      ν 1750, 1650,                                                              1480, 1420, 1380,                                                             1200, 1110               __________________________________________________________________________

EXAMPLE 7 3-hydroxy-4-[(N-methyl-N-pheyl)scarbamoyl]phenyl ester ofpivalic acid ##STR245##

The mixture of methanol (5 ml) and triethylamine (0.3 ml) of thecompound (83 mg) of the present invention obtained by procedure ofExample 2 (112) was stirred for 3 hours at room temperature.

The reaction solution was extracted with ether, and the extract waswashed successively with 1N-HCl, water, saturated an aqueous solution ofsodium chloride.

The solution was dried with sodium sulfate, and distilled off underreduced pressure to give the title compound (68 mg) having the followingphysical data.

TLC: Rf 0.34 (methylene chloride: ethyl acetate=30:1);

NMR (CDCl3): δ 7.0˜7.4(6 H, m), 6.65(1 H,d), 6.1(1 H,2 d), 3.5(3 H,s),1.3(9 H,s).

EXAMPLES OF PREPARATIONS

The following components were admixed in conventional method and punchedout to obtain 100 tablets each containing 50 mg of active ingredient.

N-[o-(p-pivaloyloxybenzene) . . . 5 g

sulfonylaminobenzoyl)glyctne

Cellulose calcium glycolate . . . 0.2 g

(disintegrating agent)

Magnesium stearate . . . 0.1 g

(lubricating agent)

Microcrystaltne cellulose . . . 4.7 g

What is claimed is:
 1. A compound of the formula: ##STR246## wherein Yrepresents sulfonyl (--SO₂) or carbonyl ##STR247## one of R¹ and R²represents (1) hydrogen or(2) an alkyl of up to 16 carbon atoms or a2-carboxyethyl and the other of R¹ and R² represents a group of theformula: --X--(R⁴)n whereinX represents a single-bond, sulfonyl (--SO₂),an alkylene of up to 4 carbon atoms, an alkylene of up to 4 carbon atomsunsubstituted or substituted by --COOH, or benzyloxycarbonyl ##STR248##--A-- represent a pyridine or pyrrole ring, n represents an integer of 1or 2, R⁴, which may be the same or different, represents(1) hydrogen, oran alkyl group of up to 8 carbon atoms, (2) a group of the formula:--Z⁴¹ --COOR⁴³ whereinZ⁴¹ represent a single-bond, an alkylene of up to4 carbon toms, or an alkenylene of from 2 to 4 carbon atoms, and R⁴³represents hydrogen, an alkyl of up to 4 carbon atoms or benzyl, R³represents(1) hydrogen, (2) hydroxy, (3) an alkyl of up to 6carbonatoms, (4) halogen, (5) an alkoxy of up to 4 carbon atoms, (6) anacyloxy of 2 to 5 carbon atoms, m represents an integer of 1 or 2,or apharmaceutically acceptable salt thereof.
 2. A compound according toclaim 1, wherein A is a pyridine ring.
 3. A compound according to claim2, which is selected from the group consistingof:p-[N-(α-pyridyl)sulfamoyl]phenyl ester of pivalic acid,p-[N-(β-pyridyl)sulfamoyl]phenyl ester of pivalic acid,p-[N-(4-pyridyl)sulfamoyl]phenyl ester of pivalic acid,2-methyl-4[N-(3-carboxypyridine-2-yl)sulfamoyl]phenyl ester of pivalicacid, p-[N-(α-pyridylmethyl)sulfamoyl]phenyl ester of pivalic acid,p-[N-(β-pyridylmethyl)sulfamoyl]phenyl ester of pivalic acid,p-[N-(4-pyridylmethyl)sulfamoyl]phenyl ester of pivalic acid,
 4. Acompound according to claim 3, which is:p-[N-(α-pyridyl)sulfamoyl]phenylester of pivalic acid.
 5. A compound according to claim 1, wherein Y issulfonyl (--SO₂ --).
 6. A pharmaceutical composition for the treatmentof pulmonary emphysema, atherosclerosis and rheumatoid arthritis, whichcomprises, as active ingredient, an effective amount of at least onecompound of the formula (I) depicted in claim 1, wherein various symbolsare as defined in claim 1, together with a pharmaceutically acceptablecarrier.
 7. A method for the treatment of pulmonary emphysema,atherosclerosis and rheumatoid arthritis comprising administering to apatient in need of same, a pharmaceutical composition which comprises,as active ingredient, an effective amount of at least one compound ofthe formula (I) of claim 1.